Ribonuclease H

Last updated
ribonuclease H
RNase H fix.png
Crystallographic structure of E. coli RNase HI. [1]
Identifiers
EC no. 3.1.26.4
CAS no. 9050-76-4
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
Search
PMC articles
PubMed articles
NCBI proteins
retroviral ribonuclease H
Identifiers
EC no. 3.1.26.13
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Search
PMC articles
PubMed articles
NCBI proteins

Ribonuclease H (abbreviated RNase H or RNH) is a family of non-sequence-specific endonuclease enzymes that catalyze the cleavage of RNA in an RNA/DNA substrate via a hydrolytic mechanism. Members of the RNase H family can be found in nearly all organisms, from bacteria to archaea to eukaryotes.

Contents

The family is divided into evolutionarily related groups with slightly different substrate preferences, broadly designated ribonuclease H1 and H2. [2] The human genome encodes both H1 and H2. Human ribonuclease H2 is a heterotrimeric complex composed of three subunits, mutations in any of which are among the genetic causes of a rare disease known as Aicardi–Goutières syndrome. [3] A third type, closely related to H2, is found only in a few prokaryotes, [4] whereas H1 and H2 occur in all domains of life. [4] Additionally, RNase H1-like retroviral ribonuclease H domains occur in multidomain reverse transcriptase proteins, which are encoded by retroviruses such as HIV and are required for viral replication. [5] [6]

In eukaryotes, ribonuclease H1 is involved in DNA replication of the mitochondrial genome. Both H1 and H2 are involved in genome maintenance tasks such as processing of R-loop structures. [2] [7]

Classification and nomenclature

Ribonuclease H is a family of endonuclease enzymes with a shared substrate specificity for the RNA strand of RNA-DNA duplexes. By definition, RNases H cleave RNA backbone phosphodiester bonds to leave a 3' hydroxyl and a 5' phosphate group. [7] RNases H have been proposed as members of an evolutionarily related superfamily encompassing other nucleases and nucleic acid processing enzymes such as retroviral integrases, DNA transposases, Holliday junction resolvases, Piwi and Argonaute proteins, various exonucleases, and the spliceosomal protein Prp8. [8] [9]

RNases H can be broadly divided into two subtypes, H1 and H2, which for historical reasons are given Arabic numeral designations in eukaryotes and Roman numeral designations in prokaryotes. Thus the Escherichia coli RNase HI is a homolog of the Homo sapiens RNase H1. [2] [7] In E. coli and many other prokaryotes, the rnhA gene encodes HI and the rnhB gene encodes HII. A third related class, called HIII, occurs in a few bacteria and archaea; it is closely related to prokaryotic HII enzymes. [4]

Structure

Comparison of the structures of representative ribonuclease H proteins from each subtype. In the E. coli protein (beige, top left), the four conserved active site residues are shown as spheres. In the H. sapiens proteins, the structural core common between the H1 and H2 subtypes is shown in red. Structures are rendered from: E. coli, PDB: 2RN2 ; T. maritima, PDB: 303F ; B. stearothermophilus, PDB: 2D0B ; H. sapiens H1, PDB: 2QK9 ; H. sapiens, PDB: 3P56 . Ribonuclease H structure comparison.png
Comparison of the structures of representative ribonuclease H proteins from each subtype. In the E. coli protein (beige, top left), the four conserved active site residues are shown as spheres. In the H. sapiens proteins, the structural core common between the H1 and H2 subtypes is shown in red. Structures are rendered from: E. coli , PDB: 2RN2 ​; T. maritima , PDB: 303F ​; B. stearothermophilus , PDB: 2D0B ​; H. sapiens H1, PDB: 2QK9 ​; H. sapiens , PDB: 3P56 ​.

The structure of RNase H commonly consists of a 5-stranded β-sheet surrounded by a distribution of α-helices. [10] All RNases H have an active site centered on a conserved sequence motif composed of aspartate and glutamate residues, often referred to as the DEDD motif. These residues interact with catalytically required magnesium ions. [7] [5]

RNases H2 are larger than H1 and usually have additional helices. The domain organization of the enzymes varies; some prokaryotic and most eukaryotic members of the H1 group have an additional small domain at the N-terminus known as the "hybrid binding domain", which facilitates binding to RNA:DNA hybrid duplexes and sometimes confers increased processivity. [2] [7] [11] While all members of the H1 group and the prokaryotic members of the H2 group function as monomers, eukaryotic H2 enzymes are obligate heterotrimers. [2] [7] Prokaryotic HIII enzymes are members of the broader H2 group and share most structural features with H2, with the addition of an N-terminal TATA box binding domain. [7] Retroviral RNase H domains occurring in multidomain reverse transcriptase proteins have structures closely resembling the H1 group. [5]

RNases H1 have been extensively studied to explore the relationships between structure and enzymatic activity. They are also used, especially the E. coli homolog, as model systems to study protein folding. [12] [13] [14] Within the H1 group, a relationship has been identified between higher substrate-binding affinity and the presence of structural elements consisting of a helix and flexible loop providing a larger and more basic substrate-binding surface. The C-helix has a scattered taxonomic distribution; it is present in the E. coli and human RNase H1 homologs and absent in the HIV RNase H domain, but examples of retroviral domains with C-helices do exist. [15] [16]

Function

Ribonuclease H enzymes cleave the phosphodiester bonds of RNA in a double-stranded RNA:DNA hybrid, leaving a 3' hydroxyl and a 5' phosphate group on either end of the cut site with a two-metal-ion catalysis mechanism, in which two divalent cations, such as Mg2+ and Mn2+, directly participate in the catalytic function. [17] Depending on the differences in their amino acid sequences, these RNases H are classified into type 1 and type 2 RNases H. [7] [18] Type 1 RNases H have prokaryotic and eukaryotic RNases H1 and retroviral RNase H. Type 2 RNases H have prokaryotic and eukaryotic RNases H2 and bacterial RNase H3. These RNases H exist in a monomeric form, except for eukaryotic RNases H2, which exist in a heterotrimeric form. [19] [20] RNase H1 and H2 have distinct substrate preferences and distinct but overlapping functions in the cell. In prokaryotes and lower eukaryotes, neither enzyme is essential, whereas both are believed to be essential in higher eukaryotes. [2] The combined activity of both H1 and H2 enzymes is associated with maintenance of genome stability due to the enzymes' degradation of the RNA component of R-loops. [21] [22]

Ribonuclease H1

Identifiers
SymbolRNase H
Pfam PF00075
Pfam clan CL0219
InterPro IPR002156
PROSITE PS50879
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Ribonuclease H1 enzymes require at least four ribonucleotide-containing base pairs in a substrate and cannot remove a single ribonucleotide from a strand that is otherwise composed of deoxyribonucleotides. For this reason, it is considered unlikely that RNase H1 enzymes are involved in the processing of RNA primers from Okazaki fragments during DNA replication. [2] RNase H1 is not essential in unicellular organisms where it has been investigated; in E. coli , RNase H1 knockouts confer a temperature-sensitive phenotype, [7] and in S. cerevisiae , they produce defects in stress response. [23]

In many eukaryotes, including mammals, RNase H1 genes include a mitochondrial targeting sequence, leading to expression of isoforms with and without the MTS present. As a result, RNase H1 is localized to both mitochondria and the nucleus. In knockout mouse models, RNase H1-null mutants are lethal during embryogenesis due to defects in replicating mitochondrial DNA. [2] [24] [25] The defects in mitochondrial DNA replication induced by loss of RNase H1 are likely due to defects in R-loop processing. [22]

Ribonuclease H2

Identifiers
SymbolRNase HII
Pfam PF01351
Pfam clan CL0219
InterPro IPR024567
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

In prokaryotes, RNase H2 is enzymatically active as a monomeric protein. In eukaryotes, it is an obligate heterotrimer composed of a catalytic subunit A and structural subunits B and C. While the A subunit is closely homologous to the prokaryotic RNase H2, the B and C subunits have no apparent homologs in prokaryotes and are poorly conserved at the sequence level even among eukaryotes. [26] [27] The B subunit mediates protein-protein interactions between the H2 complex and PCNA, which localizes H2 to replication foci. [28]

Both prokaryotic and eukaryotic H2 enzymes can cleave single ribonucleotides in a strand. [2] however, they have slightly different cleavage patterns and substrate preferences: prokaryotic enzymes have lower processivity and hydrolyze successive ribonucleotides more efficiently than ribonucleotides with a 5' deoxyribonucleotide, while eukaryotic enzymes are more processive and hydrolyze both types of substrate with similar efficiency. [2] [27] The substrate specificity of RNase H2 gives it a role in ribonucleotide excision repair, removing misincorporated ribonucleotides from DNA, in addition to R-loop processing. [29] [30] [28] Although both H1 and H2 are present in the mammalian cell nucleus, H2 is the dominant source of RNase H activity there and is important for maintaining genome stability. [28]

Some prokaryotes possess an additional H2-type gene designated RNase HIII in the Roman-numeral nomenclature used for the prokaryotic genes. HIII proteins are more closely related to the H2 group by sequence identity and structural similarity, but have substrate preferences that more closely resemble H1. [7] [31] Unlike HI and HII, which are both widely distributed among prokaryotes, HIII is found in only a few organisms with a scattered taxonomic distribution; it is somewhat more common in archaea and is rarely or never found in the same prokaryotic genome as HI. [32]

Mechanism

Reaction mechanism for RNase H catalysis using two metal ions in the HIV-1 RNase H domain RNaseH active site.svg
Reaction mechanism for RNase H catalysis using two metal ions in the HIV-1 RNase H domain

The active site of nearly all RNases H contains four negatively charged amino acid residues, known as the DEDD motif; often a histidine e.g. in HIV-1, human or E. coli is also present. [2] [7]

The charged residues bind two metal ions that are required for catalysis; under physiological conditions these are magnesium ions, but manganese also usually supports enzymatic activity, [2] [7] while calcium or high concentration of Mg2+ inhibits activity. [11] [33] [34]

Based on experimental evidence and computer simulations the enzyme activates a water molecule bound to one of the metal ions with the conserved histidine. [33] [35] The transition state is associative in nature [17] and forms an intermediate with protonated phosphate and deprotonated alkoxide leaving group. [35] The leaving group is protonated via the glutamate which has an elevated pKa and is likely to be protonated. The mechanism is similar to RNase T and the RuvC subunit in the Cas9 enzyme which both also use a histidine and a two-metal ion mechanism.

The mechanism of the release of the cleaved product is still unresolved. Experimental evidence from time-resolved crystallography and similar nucleases points to a role of a third ion in the reaction recruited to the active site. [36] [37]

In human biology

The human genome contains four genes encoding RNase H:

In addition, genetic material of retroviral origin appears frequently in the genome, reflecting integration of the genomes of human endogenous retroviruses. Such integration events result in the presence of genes encoding retroviral reverse transcriptase, which includes an RNase H domain. An example is ERVK6. [38] Long terminal repeat (LTR) and non-long terminal repeat (non-LTR) retrotransposons are also common in the genome and often include their own RNase H domains, with a complex evolutionary history. [39] [40] [41]

Role in disease

The structure of the trimeric human H2 complex, with the catalytic A subunit in blue, the structural B subunit in brown, and the structural C subunit in pink. Although the B and C subunits do not interact with the active site, they are required for activity. The catalytic residues in the active site are shown in magenta. Positions shown in yellow are those with known AGS mutations. The most common AGS mutation - alanine to threonine at position 177 of subunit B - is shown as a green sphere. Many of these mutations do not disrupt catalytic activity in vitro, but do destabilize the complex or interfere with protein-protein interactions with other proteins in the cell. 3puf rnaseH2 AGS mutations.png
The structure of the trimeric human H2 complex, with the catalytic A subunit in blue, the structural B subunit in brown, and the structural C subunit in pink. Although the B and C subunits do not interact with the active site, they are required for activity. The catalytic residues in the active site are shown in magenta. Positions shown in yellow are those with known AGS mutations. The most common AGS mutation - alanine to threonine at position 177 of subunit B - is shown as a green sphere. Many of these mutations do not disrupt catalytic activity in vitro, but do destabilize the complex or interfere with protein-protein interactions with other proteins in the cell.

In small studies, mutations in human RNase H1 have been associated with chronic progressive external ophthalmoplegia, a common feature of mitochondrial disease. [25]

Mutations in any of the three RNase H2 subunits are well-established as causes of a rare genetic disorder known as Aicardi–Goutières syndrome (AGS), [3] which manifests as neurological and dermatological symptoms at an early age. [43] The symptoms of AGS closely resemble those of congenital viral infection and are associated with inappropriate upregulation of type I interferon. AGS can also be caused by mutations in other genes: TREX1, SAMHD1, ADAR, and MDA5/IFIH1, all of which are involved in nucleic acid processing. [44] Characterization of mutational distribution in an AGS patient population found 5% of all AGS mutations in RNASEH2A, 36% in 2B, and 12% in 2C. [45] Mutations in 2B have been associated with somewhat milder neurological impairment [46] and with an absence of interferon-induced gene upregulation that can be detected in patients with other AGS-associated genotypes. [44]

In viruses

The crystal structure of the HIV reverse transcriptase heterodimer (yellow and green), with the RNase H domain shown in blue (active site in magenta spheres). The orange nucleic acid strand is RNA, the red strand is DNA. 1hys hiv RT highlight rnh.png
The crystal structure of the HIV reverse transcriptase heterodimer (yellow and green), with the RNase H domain shown in blue (active site in magenta spheres). The orange nucleic acid strand is RNA, the red strand is DNA.

Two groups of viruses use reverse transcription as part of their life cycles: retroviruses, which encode their genomes in single-stranded RNA and replicate through a double-stranded DNA intermediate; and dsDNA-RT viruses, which replicate their double-stranded DNA genomes through an RNA "pregenome" intermediate. Pathogenic examples include human immunodeficiency virus and hepatitis B virus, respectively. Both encode large multifunctional reverse transcriptase (RT) proteins containing RNase H domains. [48] [49]

Retroviral RT proteins from HIV-1 and murine leukemia virus are the best-studied members of the family. [50] [51] Retroviral RT is responsible for converting the virus' single-stranded RNA genome into double-stranded DNA. This process requires three steps: first, RNA-dependent DNA polymerase activity produces minus-strand DNA from the plus-strand RNA template, generating an RNA:DNA hybrid intermediate; second, the RNA strand is destroyed; and third, DNA-dependent DNA polymerase activity synthesizes plus-strand DNA, generating double-stranded DNA as the final product. The second step of this process is carried out by an RNase H domain located at the C-terminus of the RT protein. [5] [6] [52] [53]

RNase H performs three types of cleaving actions: non-specific degradation of the plus-strand RNA genome, specific removal of the minus-strand tRNA primer, and removal of the plus-strand purine-rich polypurine tract (PPT) primer. [54] RNase H plays a role in the priming of the plus-strand, but not in the conventional method of synthesizing a new primer sequence. Rather RNase H creates a "primer" from the PPT that is resistant to RNase H cleavage. By removing all bases but the PPT, the PPT is used as a marker for the end of the U3 region of its long terminal repeat. [53]

Because RNase H activity is required for viral proliferation, this domain has been considered a drug target for the development of antiretroviral drugs used in the treatment of HIV/AIDS and other conditions caused by retroviruses. Inhibitors of retroviral RNase H of several different chemotypes have been identified, many of which have a mechanism of action based on chelation of the active-site cations. [55] Reverse-transcriptase inhibitors that specifically inhibit the polymerase function of RT are in widespread clinical use, but not inhibitors of the RNase H function; it is the only enzymatic function encoded by HIV that is not yet targeted by drugs in clinical use. [52] [56]

Evolution

RNases H are widely distributed and occur in all domains of life. The family belongs to a larger superfamily of nuclease enzymes [8] [9] and is considered to be evolutionarily ancient. [57] In prokaryotic genomes, multiple RNase H genes are often present, but there is little correlation between occurrence of HI, HII, and HIII genes and overall phylogenetic relationships, suggesting that horizontal gene transfer may have played a role in establishing the distribution of these enzymes. RNase HI and HIII rarely or never appear in the same prokaryotic genome. When an organism's genome contains more than one RNase H gene, they sometimes have significant differences in activity level. These observations have been suggested to reflect an evolutionary pattern that minimizes functional redundancy among RNase H genes. [7] [32] RNase HIII, which is unique to prokaryotes, has a scattered taxonomic distribution and is found in both bacteria and archaea; [32] it is believed to have diverged from HII fairly early. [58]

The evolutionary trajectory of RNase H2 in eukaryotes, especially the mechanism by which eukaryotic homologs became obligate heterotrimers, is unclear; the B and C subunits have no apparent homologs in prokaryotes. [2] [27]

Applications

Because RNase H specifically degrades only the RNA in double-stranded RNA:DNA hybrids, it is commonly used as a laboratory reagent in molecular biology. Purified preparations of E. coli RNase HI and HII are commercially available. RNase HI is often used to destroy the RNA template after first-strand complementary DNA (cDNA) synthesis by reverse transcription. It can also be used to cleave specific RNA sequences in the presence of short complementary segments of DNA. [59] Highly sensitive techniques such as surface plasmon resonance can be used for detection. [60] [61] RNase HII can be used to degrade the RNA primer component of an Okazaki fragment or to introduce single-stranded nicks at positions containing a ribonucleotide. [59] A variant of hot start PCR, known as RNase H-dependent PCR or rhPCR, has been described using a thermostable RNase HII from the hyperthermophilic archaeon Pyrococcus abyssi . [62] Of note, the ribonuclease inhibitor protein commonly used as a reagent is not effective at inhibiting the activity of either HI or HII. [59]

History

Ribonucleases H were first discovered in the laboratory of Peter Hausen when researchers found RNA:DNA hybrid endonuclease activity in calf thymus in 1969 and gave it the name "ribonuclease H" to designate its hybrid specificity. [26] [63] [64] RNase H activity was subsequently discovered in E. coli [65] and in a sample of oncoviruses with RNA genomes during early studies of viral reverse transcription. [66] [67] It later became clear that calf thymus extract contained more than one protein with RNase H activity [68] and that E. coli contained two RNase H genes. [69] [70] Originally, the enzyme now known as RNase H2 in eukaryotes was designated H1 and vice versa, but the names of the eukaryotic enzymes were switched to match those in E. coli to facilitate comparative analysis, yielding the modern nomenclature in which the prokaryotic enzymes are designated with Roman numerals and the eukaryotic enzymes with Arabic numerals. [2] [26] [31] [71] The prokaryotic RNase HIII, reported in 1999, was the last RNase H subtype to be identified. [31]

Characterizing eukaryotic RNase H2 was historically a challenge, in part due to its low abundance. [2] Careful efforts at purification of the enzyme suggested that, unlike the E. coli RNase H2, the eukaryotic enzyme had multiple subunits. [72] The S. cerevisiae homolog of the E. coli protein (that is, the H2A subunit) was easily identifiable by bioinformatics when the yeast genome was sequenced, [73] but the corresponding protein was found not to have enzymatic activity in isolation. [2] [23] Eventually, the yeast B and C subunits were isolated by co-purification and found to be required for enzymatic activity. [74] However, the yeast B and C subunits have very low sequence identity to their homologs in other organisms, and the corresponding human proteins were conclusively identified only after mutations in all three were found to cause Aicardi–Goutières syndrome. [2] [3]

Related Research Articles

<span class="mw-page-title-main">Retrovirus</span> Family of viruses

A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds.

<span class="mw-page-title-main">Reverse transcriptase</span> Enzyme which generates DNA

A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, by retrotransposon mobile genetic elements to proliferate within the host genome, and by eukaryotic cells to extend the telomeres at the ends of their linear chromosomes. Contrary to a widely held belief, the process does not violate the flows of genetic information as described by the classical central dogma, as transfers of information from RNA to DNA are explicitly held possible.

<span class="mw-page-title-main">Ribonuclease</span> Class of enzyme that catalyzes the degradation of RNA

Ribonuclease is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the EC 2.7 and 3.1 classes of enzymes.

<span class="mw-page-title-main">Retrotransposon</span> Type of genetic component

Retrotransposons are a type of genetic component that copy and paste themselves into different genomic locations (transposon) by converting RNA back into DNA through the reverse transcription process using an RNA transposition intermediate.

<span class="mw-page-title-main">Ribonuclease P</span> Class of enzymes

Ribonuclease P is a type of ribonuclease which cleaves RNA. RNase P is unique from other RNases in that it is a ribozyme – a ribonucleic acid that acts as a catalyst in the same way that a protein-based enzyme would. Its function is to cleave off an extra, or precursor, sequence of RNA on tRNA molecules. Further, RNase P is one of two known multiple turnover ribozymes in nature, the discovery of which earned Sidney Altman and Thomas Cech the Nobel Prize in Chemistry in 1989: in the 1970s, Altman discovered the existence of precursor tRNA with flanking sequences and was the first to characterize RNase P and its activity in processing of the 5' leader sequence of precursor tRNA. Recent findings also reveal that RNase P has a new function. It has been shown that human nuclear RNase P is required for the normal and efficient transcription of various small noncoding RNAs, such as tRNA, 5S rRNA, SRP RNA and U6 snRNA genes, which are transcribed by RNA polymerase III, one of three major nuclear RNA polymerases in human cells.

<span class="mw-page-title-main">Ribonuclease III</span> Class of enzymes

Ribonuclease III (RNase III or RNase C)(BRENDA 3.1.26.3) is a type of ribonuclease that recognizes dsRNA and cleaves it at specific targeted locations to transform them into mature RNAs. These enzymes are a group of endoribonucleases that are characterized by their ribonuclease domain, which is labelled the RNase III domain. They are ubiquitous compounds in the cell and play a major role in pathways such as RNA precursor synthesis, RNA Silencing, and the pnp autoregulatory mechanism.

<span class="mw-page-title-main">Multicopy single-stranded DNA</span>

Multicopy single-stranded DNA (msDNA) is a type of extrachromosomal satellite DNA that consists of a single-stranded DNA molecule covalently linked via a 2'-5'phosphodiester bond to an internal guanosine of an RNA molecule. The resultant DNA/RNA chimera possesses two stem-loops joined by a branch similar to the branches found in RNA splicing intermediates. The coding region for msDNA, called a "retron", also encodes a type of reverse transcriptase, which is essential for msDNA synthesis.

The degradosome is a multiprotein complex present in most bacteria that is involved in the processing of ribosomal RNA and the degradation of messenger RNA and is regulated by Non-coding RNA. It contains the proteins RNA helicase B, RNase E and Polynucleotide phosphorylase.

<span class="mw-page-title-main">TREX1</span> Protein-coding gene in the species Homo sapiens

Three prime repair exonuclease 1 is an enzyme that in humans is encoded by the TREX1 gene.

<span class="mw-page-title-main">POP7</span> Protein-coding gene in the species Homo sapiens

Ribonuclease P protein subunit p20 is an enzyme that in humans is encoded by the POP7 gene.

<span class="mw-page-title-main">RPP14</span> Protein-coding gene in the species Homo sapiens

Ribonuclease P protein subunit p14 is an enzyme that in humans is encoded by the RPP14 gene.

<span class="mw-page-title-main">SAMHD1</span>

SAM domain and HD domain-containing protein 1 is a protein that in humans is encoded by the SAMHD1 gene. SAMHD1 is a cellular enzyme, responsible for blocking replication of HIV in dendritic cells, macrophages, monocytes and resting CD4+ T lymphocytes. It is an enzyme that exhibits phosphohydrolase activity, converting deoxynucleoside triphosphates (dNTPs) to inorganic phosphate (iPPP) and a 2'-deoxynucleoside (i.e. deoxynucleosides without a phosphate group). In doing so, SAMHD1 depletes the pool of dNTPs available to a reverse transcriptase for viral cDNA synthesis and thus prevents viral replication. SAMHD1 has also shown nuclease activity. Although a ribonuclease activity was described to be required for HIV-1 restriction, recent data confirmed that SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease activity.

<span class="mw-page-title-main">RNASEH1</span> Protein-coding gene in the species Homo sapiens

Ribonuclease H1 also known as RNase H1 is an enzyme that in humans is encoded by the RNASEH1 gene. The RNase H1 is a non-specific endonuclease and catalyzes the cleavage of RNA via a hydrolytic mechanism.

<span class="mw-page-title-main">RNASEH2A</span> Protein-coding gene in the species Homo sapiens

Ribonuclease H2 subunit A, also known as RNase H2 subunit A, is an enzyme that in humans is encoded by the RNASEH2A gene.

<span class="mw-page-title-main">RNASEH2B</span> Protein-coding gene in the species Homo sapiens

Ribonuclease H2, subunit B is a protein that in humans is encoded by the RNASEH2B gene. RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits, and degrades the RNA of RNA:DNA hybrids. The non-catalytic B subunit of RNase H2 is thought to play a role in DNA replication.

<span class="mw-page-title-main">Aicardi–Goutières syndrome</span> Medical condition

Aicardi–Goutières syndrome (AGS), which is completely distinct from the similarly named Aicardi syndrome, is a rare, usually early onset childhood, inflammatory disorder most typically affecting the brain and the skin. The majority of affected individuals experience significant intellectual and physical problems, although this is not always the case. The clinical features of AGS can mimic those of in utero acquired infection, and some characteristics of the condition also overlap with the autoimmune disease systemic lupus erythematosus (SLE). Following an original description of eight cases in 1984, the condition was first referred to as 'Aicardi–Goutières syndrome' (AGS) in 1992, and the first international meeting on AGS was held in Pavia, Italy, in 2001.

Ribonuclease E is a bacterial ribonuclease that participates in the processing of ribosomal RNA and the chemical degradation of bulk cellular RNA.

<span class="mw-page-title-main">Retroviral ribonuclease H</span>

The retroviral ribonuclease H is a catalytic domain of the retroviral reverse transcriptase (RT) enzyme. The RT enzyme is used to generate complementary DNA (cDNA) from the retroviral RNA genome. This process is called reverse transcription. To complete this complex process, the retroviral RT enzymes need to adopt a multifunctional nature. They therefore possess 3 of the following biochemical activities: RNA-dependent DNA polymerase, ribonuclease H, and DNA-dependent DNA polymerase activities. Like all RNase H enzymes, the retroviral RNase H domain cleaves DNA/RNA duplexes and will not degrade DNA or unhybridized RNA.

<span class="mw-page-title-main">Ribonuclease T</span>

Ribonuclease T is a ribonuclease enzyme involved in the maturation of transfer RNA and ribosomal RNA in bacteria, as well as in DNA repair pathways. It is a member of the DnaQ family of exonucleases and non-processively acts on the 3' end of single-stranded nucleic acids. RNase T is capable of cleaving both DNA and RNA, with extreme sequence specificity discriminating against cytosine at the 3' end of the substrate.

<span class="mw-page-title-main">RNASEH2C</span> Protein-coding gene in the species Homo sapiens

Ribonuclease H2 subunit C is a protein that in humans is encoded by the RNASEH2C gene. RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits, and degrades the RNA of RNA:DNA hybrids.

References

  1. ↑ PDB: 1JL1 ​; Goedken ER, Marqusee S (December 2001). "Native-state energetics of a thermostabilized variant of ribonuclease HI". Journal of Molecular Biology. 314 (4): 863–71. doi:10.1006/jmbi.2001.5184. PMID   11734003.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Cerritelli SM, Crouch RJ (March 2009). "Ribonuclease H: the enzymes in eukaryotes". The FEBS Journal. 276 (6): 1494–505. doi:10.1111/j.1742-4658.2009.06908.x. PMC   2746905 . PMID   19228196.
  3. 1 2 3 Crow YJ, Leitch A, Hayward BE, Garner A, Parmar R, Griffith E, et al. (August 2006). "Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection". Nature Genetics. 38 (8): 910–6. doi:10.1038/ng1842. PMID   16845400. S2CID   8076225.
  4. 1 2 3 Figiel M, Nowotny M (August 2014). "Crystal structure of RNase H3-substrate complex reveals parallel evolution of RNA/DNA hybrid recognition". Nucleic Acids Research. 42 (14): 9285–94. doi:10.1093/nar/gku615. PMC   4132731 . PMID   25016521.
  5. 1 2 3 4 Davies JF, Hostomska Z, Hostomsky Z, Jordan SR, Matthews DA (April 1991). "Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase". Science. 252 (5002): 88–95. Bibcode:1991Sci...252...88D. doi:10.1126/science.1707186. PMID   1707186.
  6. 1 2 Hansen J, Schulze T, Mellert W, Moelling K (January 1988). "Identification and characterization of HIV-specific RNase H by monoclonal antibody". The EMBO Journal. 7 (1): 239–43. doi:10.1002/j.1460-2075.1988.tb02805.x. PMC   454263 . PMID   2452083.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 13 Tadokoro T, Kanaya S (March 2009). "Ribonuclease H: molecular diversities, substrate binding domains, and catalytic mechanism of the prokaryotic enzymes". The FEBS Journal. 276 (6): 1482–93. doi:10.1111/j.1742-4658.2009.06907.x. PMID   19228197. S2CID   29008571.
  8. 1 2 Majorek KA, Dunin-Horkawicz S, Steczkiewicz K, Muszewska A, Nowotny M, Ginalski K, Bujnicki JM (April 2014). "The RNase H-like superfamily: new members, comparative structural analysis and evolutionary classification". Nucleic Acids Research. 42 (7): 4160–79. doi:10.1093/nar/gkt1414. PMC   3985635 . PMID   24464998.
  9. 1 2 Rice P, Craigie R, Davies DR (February 1996). "Retroviral integrases and their cousins". Current Opinion in Structural Biology. 6 (1): 76–83. doi:10.1016/s0959-440x(96)80098-4. PMID   8696976.
  10. ↑ Schmitt TJ, Clark JE, Knotts TA (December 2009). "Thermal and mechanical multistate folding of ribonuclease H". The Journal of Chemical Physics. 131 (23): 235101. Bibcode:2009JChPh.131w5101S. doi:10.1063/1.3270167. PMID   20025349.
  11. 1 2 Nowotny M, Cerritelli SM, Ghirlando R, Gaidamakov SA, Crouch RJ, Yang W (April 2008). "Specific recognition of RNA/DNA hybrid and enhancement of human RNase H1 activity by HBD". The EMBO Journal. 27 (7): 1172–81. doi:10.1038/emboj.2008.44. PMC   2323259 . PMID   18337749.
  12. ↑ Cecconi C, Shank EA, Bustamante C, Marqusee S (September 2005). "Direct observation of the three-state folding of a single protein molecule". Science. 309 (5743): 2057–60. Bibcode:2005Sci...309.2057C. doi:10.1126/science.1116702. PMID   16179479. S2CID   43823877.
  13. ↑ Hollien J, Marqusee S (March 1999). "A thermodynamic comparison of mesophilic and thermophilic ribonucleases H". Biochemistry. 38 (12): 3831–6. doi:10.1021/bi982684h. PMID   10090773.
  14. ↑ Raschke TM, Marqusee S (April 1997). "The kinetic folding intermediate of ribonuclease H resembles the acid molten globule and partially unfolded molecules detected under native conditions". Nature Structural Biology. 4 (4): 298–304. doi:10.1038/nsb0497-298. PMID   9095198. S2CID   33673059.
  15. ↑ Schultz SJ, Champoux JJ (June 2008). "RNase H activity: structure, specificity, and function in reverse transcription". Virus Research. 134 (1–2): 86–103. doi:10.1016/j.virusres.2007.12.007. PMC   2464458 . PMID   18261820.
  16. ↑ Champoux JJ, Schultz SJ (March 2009). "Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription". The FEBS Journal. 276 (6): 1506–16. doi:10.1111/j.1742-4658.2009.06909.x. PMC   2742777 . PMID   19228195.
  17. 1 2 Yang W, Lee JY, Nowotny M (April 2006). "Making and breaking nucleic acids: two-Mg2+-ion catalysis and substrate specificity". Molecular Cell. 22 (1): 5–13. doi: 10.1016/j.molcel.2006.03.013 . PMID   16600865.
  18. ↑ Ohtani N, Haruki M, Morikawa M, Kanaya S (January 1999). "Molecular diversities of RNases H". Journal of Bioscience and Bioengineering. 88 (1): 12–9. doi:10.1016/s1389-1723(99)80168-6. PMID   16232566.
  19. ↑ Bubeck D, Reijns MA, Graham SC, Astell KR, Jones EY, Jackson AP (May 2011). "PCNA directs type 2 RNase H activity on DNA replication and repair substrates". Nucleic Acids Research. 39 (9): 3652–66. doi:10.1093/nar/gkq980. PMC   3089482 . PMID   21245041.
  20. ↑ Figiel M, Chon H, Cerritelli SM, Cybulska M, Crouch RJ, Nowotny M (March 2011). "The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutières syndrome defects". The Journal of Biological Chemistry. 286 (12): 10540–50. doi: 10.1074/jbc.M110.181974 . PMC   3060507 . PMID   21177858.
  21. ↑ Amon JD, Koshland D (December 2016). "RNase H enables efficient repair of R-loop induced DNA damage". eLife. 5: e20533. doi: 10.7554/eLife.20533 . PMC   5215079 . PMID   27938663.
  22. 1 2 Lima WF, Murray HM, Damle SS, Hart CE, Hung G, De Hoyos CL, et al. (June 2016). "Viable RNaseH1 knockout mice show RNaseH1 is essential for R loop processing, mitochondrial and liver function". Nucleic Acids Research. 44 (11): 5299–312. doi:10.1093/nar/gkw350. PMC   4914116 . PMID   27131367.
  23. 1 2 Arudchandran A, Cerritelli S, Narimatsu S, Itaya M, Shin DY, Shimada Y, Crouch RJ (October 2000). "The absence of ribonuclease H1 or H2 alters the sensitivity of Saccharomyces cerevisiae to hydroxyurea, caffeine and ethyl methanesulphonate: implications for roles of RNases H in DNA replication and repair". Genes to Cells. 5 (10): 789–802. doi: 10.1046/j.1365-2443.2000.00373.x . PMID   11029655.
  24. ↑ Cerritelli SM, Frolova EG, Feng C, Grinberg A, Love PE, Crouch RJ (March 2003). "Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice". Molecular Cell. 11 (3): 807–15. doi: 10.1016/s1097-2765(03)00088-1 . PMID   12667461.
  25. 1 2 Reyes A, Melchionda L, Nasca A, Carrara F, Lamantea E, Zanolini A, et al. (July 2015). "RNASEH1 Mutations Impair mtDNA Replication and Cause Adult-Onset Mitochondrial Encephalomyopathy". American Journal of Human Genetics. 97 (1): 186–93. doi:10.1016/j.ajhg.2015.05.013. PMC   4572567 . PMID   26094573.
  26. 1 2 3 Hollis T, Shaban NM (2011-01-01). "Structure and Function of RNase H Enzymes". In Nicholson AW (ed.). Ribonucleases . Nucleic Acids and Molecular Biology. Springer Berlin Heidelberg. pp.  299–317. doi:10.1007/978-3-642-21078-5_12. ISBN   978-3-642-21077-8.
  27. 1 2 3 Chon H, Vassilev A, DePamphilis ML, Zhao Y, Zhang J, Burgers PM, et al. (January 2009). "Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex". Nucleic Acids Research. 37 (1): 96–110. doi:10.1093/nar/gkn913. PMC   2615623 . PMID   19015152.
  28. 1 2 3 Reijns MA, Jackson AP (August 2014). "Ribonuclease H2 in health and disease". Biochemical Society Transactions. 42 (4): 717–25. doi:10.1042/BST20140079. PMID   25109948.
  29. ↑ Wahba L, Amon JD, Koshland D, Vuica-Ross M (December 2011). "RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability". Molecular Cell. 44 (6): 978–88. doi:10.1016/j.molcel.2011.10.017. PMC   3271842 . PMID   22195970.
  30. ↑ Kim N, Huang SN, Williams JS, Li YC, Clark AB, Cho JE, et al. (June 2011). "Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I". Science. 332 (6037): 1561–4. Bibcode:2011Sci...332.1561K. doi:10.1126/science.1205016. PMC   3380281 . PMID   21700875.
  31. 1 2 3 Ohtani N, Haruki M, Morikawa M, Crouch RJ, Itaya M, Kanaya S (January 1999). "Identification of the genes encoding Mn2+-dependent RNase HII and Mg2+-dependent RNase HIII from Bacillus subtilis: classification of RNases H into three families". Biochemistry. 38 (2): 605–18. doi:10.1021/bi982207z. PMID   9888800.
  32. 1 2 3 Kochiwa H, Tomita M, Kanai A (July 2007). "Evolution of ribonuclease H genes in prokaryotes to avoid inheritance of redundant genes". BMC Evolutionary Biology. 7: 128. doi: 10.1186/1471-2148-7-128 . PMC   1950709 . PMID   17663799.
  33. 1 2 Alla NR, Nicholson AW (December 2012). "Evidence for a dual functional role of a conserved histidine in RNA·DNA heteroduplex cleavage by human RNase H1". FEBS Journal. 279 (24): 4492–500. doi:10.1111/febs.12035. PMC   3515698 . PMID   23078533.
  34. ↑ Rosta E, Yang W, Hummer G (February 2014). "Calcium inhibition of ribonuclease H1 two-metal ion catalysis". Journal of the American Chemical Society. 136 (8): 3137–44. doi:10.1021/ja411408x. PMC   3985467 . PMID   24499076.
  35. 1 2 Dürr S, Bohusewicz O, Berta D, Suardiaz R, Peter C, Jambrina PG, Peter C, Shao Y, Rosta E (16 June 2021). "The Role of Conserved Residues in the DEDDh Motif: the Proton-Transfer Mechanism of HIV-1 RNase H". ACS Catalysis. 11 (13): 7915–7927. doi:10.1021/acscatal.1c01493. S2CID   236285134.
  36. ↑ Gan J, Shaw G, Tropea JE, Waugh DS, Court DL, Ji X (January 2008). "A stepwise model for double-stranded RNA processing by ribonuclease III". Mol Microbiol. 67 (1): 143–54. doi: 10.1111/j.1365-2958.2007.06032.x . PMID   18047582.
  37. ↑ Samara NL, Yang W (August 2019). "Cation trafficking propels RNA hydrolysis". Nature Structural & Molecular Biology. 25 (8): 715–721. doi:10.1038/s41594-018-0099-4. PMC   6110950 . PMID   30076410.
  38. ↑ Reus K, Mayer J, Sauter M, Scherer D, Müller-Lantzsch N, Meese E (March 2001). "Genomic organization of the human endogenous retrovirus HERV-K(HML-2.HOM) (ERVK6) on chromosome 7". Genomics. 72 (3): 314–20. doi:10.1006/geno.2000.6488. PMID   11401447.
  39. ↑ Ustyantsev K, Blinov A, Smyshlyaev G (14 March 2017). "Convergence of retrotransposons in oomycetes and plants". Mobile DNA. 8 (1): 4. doi: 10.1186/s13100-017-0087-y . PMC   5348765 . PMID   28293305.
  40. ↑ Ustyantsev K, Novikova O, Blinov A, Smyshlyaev G (May 2015). "Convergent evolution of ribonuclease h in LTR retrotransposons and retroviruses". Molecular Biology and Evolution. 32 (5): 1197–207. doi:10.1093/molbev/msv008. PMC   4408406 . PMID   25605791.
  41. ↑ Malik HS (2005). "Ribonuclease H evolution in retrotransposable elements". Cytogenetic and Genome Research. 110 (1–4): 392–401. doi:10.1159/000084971. PMID   16093691. S2CID   7481781.
  42. ↑ Figiel M, Chon H, Cerritelli SM, Cybulska M, Crouch RJ, Nowotny M (March 2011). "The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutières syndrome defects". The Journal of Biological Chemistry. 286 (12): 10540–50. doi: 10.1074/jbc.M110.181974 . PMC   3060507 . PMID   21177858.
  43. ↑ Orcesi S, La Piana R, Fazzi E (2009). "Aicardi-Goutieres syndrome". British Medical Bulletin. 89: 183–201. doi: 10.1093/bmb/ldn049 . PMID   19129251.
  44. 1 2 Crow YJ, Manel N (July 2015). "Aicardi-Goutières syndrome and the type I interferonopathies". Nature Reviews. Immunology. 15 (7): 429–40. doi:10.1038/nri3850. PMID   26052098. S2CID   34259643.
  45. ↑ Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GM, Gornall HL, et al. (February 2015). "Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1". American Journal of Medical Genetics. Part A. 167A (2): 296–312. doi:10.1002/ajmg.a.36887. PMC   4382202 . PMID   25604658.
  46. ↑ Rice G, Patrick T, Parmar R, Taylor CF, Aeby A, Aicardi J, et al. (October 2007). "Clinical and molecular phenotype of Aicardi-Goutieres syndrome". American Journal of Human Genetics. 81 (4): 713–25. doi:10.1086/521373. PMC   2227922 . PMID   17846997.
  47. ↑ Sarafianos SG, Das K, Tantillo C, Clark AD, Ding J, Whitcomb JM, et al. (March 2001). "Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA". The EMBO Journal. 20 (6): 1449–61. doi:10.1093/emboj/20.6.1449. PMC   145536 . PMID   11250910.
  48. ↑ Seeger C, Mason WS (May 2015). "Molecular biology of hepatitis B virus infection". Virology. 479–480: 672–86. doi:10.1016/j.virol.2015.02.031. PMC   4424072 . PMID   25759099.
  49. ↑ Moelling K, Broecker F, Kerrigan JE (2014-01-01). "RNase H: Specificity, Mechanisms of Action, and Antiviral Target". In Vicenzi E, Poli G (eds.). Human Retroviruses. Methods in Molecular Biology. Vol. 1087. Humana Press. pp. 71–84. doi:10.1007/978-1-62703-670-2_7. ISBN   978-1-62703-669-6. PMID   24158815.
  50. ↑ Mizuno M, Yasukawa K, Inouye K (February 2010). "Insight into the mechanism of the stabilization of moloney murine leukaemia virus reverse transcriptase by eliminating RNase H activity". Bioscience, Biotechnology, and Biochemistry. 74 (2): 440–2. doi:10.1271/bbb.90777. PMID   20139597. S2CID   28110533.
  51. ↑ Coté ML, Roth MJ (June 2008). "Murine leukemia virus reverse transcriptase: structural comparison with HIV-1 reverse transcriptase". Virus Research. 134 (1–2): 186–202. doi:10.1016/j.virusres.2008.01.001. PMC   2443788 . PMID   18294720.
  52. 1 2 Nowotny M, Figiel M (2013-01-01). "The RNase H Domain: Structure, Function and Mechanism". In LeGrice S, Gotte M (eds.). Human Immunodeficiency Virus Reverse Transcriptase. Springer New York. pp. 53–75. doi:10.1007/978-1-4614-7291-9_3. ISBN   978-1-4614-7290-2.
  53. 1 2 Beilhartz GL, Götte M (April 2010). "HIV-1 Ribonuclease H: Structure, Catalytic Mechanism and Inhibitors". Viruses. 2 (4): 900–26. doi: 10.3390/v2040900 . PMC   3185654 . PMID   21994660.
  54. ↑ Klarmann GJ, Hawkins ME, Le Grice SF (2002). "Uncovering the complexities of retroviral ribonuclease H reveals its potential as a therapeutic target". AIDS Reviews. 4 (4): 183–94. PMID   12555693.
  55. ↑ Tramontano E, Di Santo R (2010). "HIV-1 RT-associated RNase H function inhibitors: Recent advances in drug development". Current Medicinal Chemistry. 17 (26): 2837–53. doi:10.2174/092986710792065045. PMID   20858167.
  56. ↑ Cao L, Song W, De Clercq E, Zhan P, Liu X (June 2014). "Recent progress in the research of small molecule HIV-1 RNase H inhibitors". Current Medicinal Chemistry. 21 (17): 1956–67. doi:10.2174/0929867321666140120121158. PMID   24438523.
  57. ↑ Ma BG, Chen L, Ji HF, Chen ZH, Yang FR, Wang L, et al. (February 2008). "Characters of very ancient proteins". Biochemical and Biophysical Research Communications. 366 (3): 607–11. doi:10.1016/j.bbrc.2007.12.014. PMID   18073136.
  58. ↑ Brindefalk B, Dessailly BH, Yeats C, Orengo C, Werner F, Poole AM (March 2013). "Evolutionary history of the TBP-domain superfamily". Nucleic Acids Research. 41 (5): 2832–45. doi:10.1093/nar/gkt045. PMC   3597702 . PMID   23376926.
  59. 1 2 3 Nichols NM, Yue D (2001-01-01). Ribonucleases. pp. Unit3.13. doi:10.1002/0471142727.mb0313s84. ISBN   978-0-471-14272-0. PMID   18972385. S2CID   221604377.{{cite book}}: |journal= ignored (help)
  60. ↑ Loo JF, Wang SS, Peng F, He JA, He L, Guo YC, et al. (July 2015). "A non-PCR SPR platform using RNase H to detect MicroRNA 29a-3p from throat swabs of human subjects with influenza A virus H1N1 infection". The Analyst. 140 (13): 4566–75. Bibcode:2015Ana...140.4566L. doi:10.1039/C5AN00679A. PMID   26000345. S2CID   28974459.
  61. ↑ Goodrich TT, Lee HJ, Corn RM (April 2004). "Direct detection of genomic DNA by enzymatically amplified SPR imaging measurements of RNA microarrays". Journal of the American Chemical Society. 126 (13): 4086–7. CiteSeerX   10.1.1.475.1922 . doi:10.1021/ja039823p. PMID   15053580.
  62. ↑ Dobosy JR, Rose SD, Beltz KR, Rupp SM, Powers KM, Behlke MA, Walder JA (August 2011). "RNase H-dependent PCR (rhPCR): improved specificity and single nucleotide polymorphism detection using blocked cleavable primers". BMC Biotechnology. 11: 80. doi: 10.1186/1472-6750-11-80 . PMC   3224242 . PMID   21831278.
  63. ↑ Stein H, Hausen P (October 1969). "Enzyme from calf thymus degrading the RNA moiety of DNA-RNA Hybrids: effect on DNA-dependent RNA polymerase". Science. 166 (3903): 393–5. Bibcode:1969Sci...166..393S. doi:10.1126/science.166.3903.393. PMID   5812039. S2CID   43683241.
  64. ↑ Hausen P, Stein H (June 1970). "Ribonuclease H. An enzyme degrading the RNA moiety of DNA-RNA hybrids". European Journal of Biochemistry. 14 (2): 278–83. doi: 10.1111/j.1432-1033.1970.tb00287.x . PMID   5506170.
  65. ↑ Miller HI, Riggs AD, Gill GN (April 1973). "Ribonuclease H (hybrid) in Escherichia coli. Identification and characterization". The Journal of Biological Chemistry. 248 (7): 2621–4. doi: 10.1016/S0021-9258(19)44152-5 . PMID   4572736.
  66. ↑ Mölling K, Bolognesi DP, Bauer H, Büsen W, Plassmann HW, Hausen P (December 1971). "Association of viral reverse transcriptase with an enzyme degrading the RNA moiety of RNA-DNA hybrids". Nature. 234 (51): 240–3. doi:10.1038/newbio234240a0. PMID   4331605.
  67. ↑ Grandgenett DP, Gerard GF, Green M (December 1972). "Ribonuclease H: a ubiquitous activity in virions of ribonucleic acid tumor viruses". Journal of Virology. 10 (6): 1136–42. doi:10.1128/jvi.10.6.1136-1142.1972. PMC   356594 . PMID   4118867.
  68. ↑ Büsen W, Hausen P (March 1975). "Distinct ribonuclease H activities in calf thymus". European Journal of Biochemistry. 52 (1): 179–90. doi: 10.1111/j.1432-1033.1975.tb03985.x . PMID   51794.
  69. ↑ Kanaya S, Crouch RJ (January 1983). "DNA sequence of the gene coding for Escherichia coli ribonuclease H". The Journal of Biological Chemistry. 258 (2): 1276–81. doi: 10.1016/S0021-9258(18)33189-2 . PMID   6296074.
  70. ↑ Itaya M (November 1990). "Isolation and characterization of a second RNase H (RNase HII) of Escherichia coli K-12 encoded by the rnhB gene". Proceedings of the National Academy of Sciences of the United States of America. 87 (21): 8587–91. Bibcode:1990PNAS...87.8587I. doi: 10.1073/pnas.87.21.8587 . PMC   55002 . PMID   2172991.
  71. ↑ Crouch RJ, Arudchandran A, Cerritelli SM (2001-01-01). "RNase H1 of Saccharomyces cerevisiae: methods and nomenclature". Ribonucleases - Part A. Methods in Enzymology. Vol. 341. pp. 395–413. doi:10.1016/s0076-6879(01)41166-9. ISBN   978-0-12-182242-2. PMID   11582793.
  72. ↑ Frank P, Braunshofer-Reiter C, Wintersberger U, Grimm R, Büsen W (October 1998). "Cloning of the cDNA encoding the large subunit of human RNase HI, a homologue of the prokaryotic RNase HII". Proceedings of the National Academy of Sciences of the United States of America. 95 (22): 12872–7. Bibcode:1998PNAS...9512872F. doi: 10.1073/pnas.95.22.12872 . PMC   23637 . PMID   9789007.
  73. ↑ Frank P, Braunshofer-Reiter C, Wintersberger U (January 1998). "Yeast RNase H(35) is the counterpart of the mammalian RNase HI, and is evolutionarily related to prokaryotic RNase HII". FEBS Letters. 421 (1): 23–6. doi:10.1016/s0014-5793(97)01528-7. PMID   9462832.
  74. ↑ Jeong HS, Backlund PS, Chen HC, Karavanov AA, Crouch RJ (2004-01-01). "RNase H2 of Saccharomyces cerevisiae is a complex of three proteins". Nucleic Acids Research. 32 (2): 407–14. doi:10.1093/nar/gkh209. PMC   373335 . PMID   14734815.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.