Kissing stem-loop

Last updated
An example of an RNA stem-loop. If now a second RNA stem-loop has complementary base-sequence, the two loops can base pair resulting in a kissing loop. Stem-loop.svg
An example of an RNA stem-loop. If now a second RNA stem-loop has complementary base-sequence, the two loops can base pair resulting in a kissing loop.
This animated GIF shows two RNA loops (orange and green) bind to each other in a structure called a kissing loop. The two RNA loops interact through stacking interactions and through hydrogen bonding (interacting bases shown in space-filling representation). Animated Base stacking.gif
This animated GIF shows two RNA loops (orange and green) bind to each other in a structure called a kissing loop. The two RNA loops interact through stacking interactions and through hydrogen bonding (interacting bases shown in space-filling representation).

In genetics, a kissing stem-loop, or kissing stem loop interaction, is formed in ribonucleic acid (RNA) when two bases between two hairpin loops pair. These intra- and intermolecular kissing interactions are important in forming the tertiary or quaternary structure of many RNAs. [2]

Contents

RNA kissing interactions, also called loop-loop pseudoknots, occur when the unpaired nucleotides in one hairpin loop, base pair with the unpaired nucleotides in another hairpin loop. [3] When the hairpin loops are located on separate RNA molecules, their intermolecular interaction is called a kissing complex. These interactions generally form between stem-loops. However, stable complexes have been observed containing only two intermolecular Watson–Crick base pairs. [4] [5]

Biological significance

RNA molecules perform their function in living cells by adopting specific and highly complex 3-dimensional structures. It is believed that recombination may be initiated by the kissing loops. Recombination is critical to successful evolution, especially in the adaptation and survival of viruses. [6] Furthermore, the kissing complex is composed of two hairpin loops that function as a regulator of CoLE1 plasmid in the E.Coli bacteria. This regulation happens when the antisense RNA of E.Coli and RNA primer responsible for DNA replication hybridizes to form the kissing complex. [7]

In retroviruses

Retroviruses are viruses that are very similar in structure, which allows them to silently replicate inside a host, keeping it alive until the replication is completed and the host is no longer needed. The genomic RNA of retroviruses is linked non-covalently to the dimer linkage structure (DLS), a non-coding region in the 5' UTR. For the kissing loop interaction to occur, there is a triple interaction that involves a 5'-flanking purine and 2 centralized bases in the complementary strand. This interaction transcripts in the major groove of the kissing loop dimer. [8]

The human immunodeficiency virus (HIV) is a retrovirus that can be transmitted via the interactions of bodily fluids. There are two types of HIV viruses, human immunodeficiency virus type 1 (HIV-1) and human immunodeficiency virus type 2 (HIV-2). From the two types of the Human Immunodeficiency Virus strain, HIV-1 is the most common strain. The RNA of the HIV-1 virus uses the kissing stem loop interaction as a means of recognition, the main step of interaction of the dimerization initiation site (DIS) to form the duplex. To study the kissing stem-loop loop interaction, It was seen that the Dimerization initiation site (DIS) complex was essential to the replication of the HIV type 1 virus in the eukaryotic cell, and any changes to the stem loop structure diminished the dimerization interaction. Experimentally, it has been seen that, in vivo, mutating the Dimerization initiation site (DIS) obstructed the dimerization of the DIS complex. [9]

See also

Related Research Articles

<span class="mw-page-title-main">HIV</span> Human retrovirus, cause of AIDS

The human immunodeficiency viruses (HIV) are two species of Lentivirus that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, the average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.

<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 (backward). 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.

An inverted repeat is a single stranded sequence of nucleotides followed downstream by its reverse complement. The intervening sequence of nucleotides between the initial sequence and the reverse complement can be any length including zero. For example, 5'---TTACGnnnnnnCGTAA---3' is an inverted repeat sequence. When the intervening length is zero, the composite sequence is a palindromic sequence.

<span class="mw-page-title-main">Stem-loop</span> Intramolecular base-pairing pattern in RNA and DNA

Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded RNA. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence when read in opposite directions, base-pair to form a double helix that ends in an unpaired loop. The resulting structure is a key building block of many RNA secondary structures. As an important secondary structure of RNA, it can direct RNA folding, protect structural stability for messenger RNA (mRNA), provide recognition sites for RNA binding proteins, and serve as a substrate for enzymatic reactions.

The genome and proteins of HIV (human immunodeficiency virus) have been the subject of extensive research since the discovery of the virus in 1983. "In the search for the causative agent, it was initially believed that the virus was a form of the Human T-cell leukemia virus (HTLV), which was known at the time to affect the human immune system and cause certain leukemias. However, researchers at the Pasteur Institute in Paris isolated a previously unknown and genetically distinct retrovirus in patients with AIDS which was later named HIV." Each virion comprises a viral envelope and associated matrix enclosing a capsid, which itself encloses two copies of the single-stranded RNA genome and several enzymes. The discovery of the virus itself occurred two years following the report of the first major cases of AIDS-associated illnesses.

<span class="mw-page-title-main">Long terminal repeat</span> DNA sequence

A long terminal repeat (LTR) is a pair of identical sequences of DNA, several hundred base pairs long, which occur in eukaryotic genomes on either end of a series of genes or pseudogenes that form a retrotransposon or an endogenous retrovirus or a retroviral provirus. All retroviral genomes are flanked by LTRs, while there are some retrotransposons without LTRs. Typically, an element flanked by a pair of LTRs will encode a reverse transcriptase and an integrase, allowing the element to be copied and inserted at a different location of the genome. Copies of such an LTR-flanked element can often be found hundreds or thousands of times in a genome. LTR retrotransposons comprise about 8% of the human genome.

<span class="mw-page-title-main">Hairpin ribozyme</span> Enzymatic section of RNA

The hairpin ribozyme is a small section of RNA that can act as a ribozyme. Like the hammerhead ribozyme it is found in RNA satellites of plant viruses. It was first identified in the minus strand of the tobacco ringspot virus (TRSV) satellite RNA where it catalyzes self-cleavage and joining (ligation) reactions to process the products of rolling circle virus replication into linear and circular satellite RNA molecules. The hairpin ribozyme is similar to the hammerhead ribozyme in that it does not require a metal ion for the reaction.

<span class="mw-page-title-main">Retroviral psi packaging element</span>

The retroviral psi packaging element, also known as the Ψ RNA packaging signal, is a cis-acting RNA element identified in the genomes of the retroviruses Human immunodeficiency virus (HIV) and Simian immunodeficiency virus (SIV). It is involved in regulating the essential process of packaging the retroviral RNA genome into the viral capsid during replication. The final virion contains a dimer of two identical unspliced copies of the viral genome.

<span class="mw-page-title-main">HIV gag stem loop 3 (GSL3)</span>

HIV gag stem loop 3 (GSL3) is a secondary structural component of the Retroviral Psi packaging element, also known as the psi recognition element. This domain plays a major role in RNA packaging and is located the 5’ untranslated region of the unspliced HIV-1 genome. GSL3 is known to direct specific packaging of HIV-1 genomic RNA. While deletion of GSL3 leads to decreases in both viral RNA packaging and dimerization, mutagenic studies have shown that it does not eliminate encapsulation of retroviral RNA.

The HIV-1 Rev response element (RRE) is a highly structured, ~350 nucleotide RNA segment present in the Env coding region of unspliced and partially spliced viral mRNAs. In the presence of the HIV-1 accessory protein Rev, HIV-1 mRNAs that contain the RRE can be exported from the nucleus to the cytoplasm for downstream events such as translation and virion packaging.

<span class="mw-page-title-main">HIV ribosomal frameshift signal</span>

HIV ribosomal frameshift signal is a ribosomal frameshift (PRF) that human immunodeficiency virus (HIV) uses to translate several different proteins from the same sequence.

<span class="mw-page-title-main">Trans-activation response element</span>

The HIV trans-activation response (TAR) element is an RNA element which is known to be required for the trans-activation of the viral promoter and for virus replication. The TAR hairpin is a dynamic structure that acts as a binding site for the Tat protein, and this interaction stimulates the activity of the long terminal repeat promoter.

<span class="mw-page-title-main">HIV-1 protease</span> Enzyme involved with peptide bond hydrolysis in retroviruses

HIV-1 protease or PR is a retroviral aspartyl protease (retropepsin), an enzyme involved with peptide bond hydrolysis in retroviruses, that is essential for the life-cycle of HIV, the retrovirus that causes AIDS. HIV-1 PR cleaves newly synthesized polyproteins at nine cleavage sites to create the mature protein components of an HIV virion, the infectious form of a virus outside of the host cell. Without effective HIV-1 PR, HIV virions remain uninfectious.

<span class="mw-page-title-main">TARBP2</span> Protein

RISC-loading complex subunit TARBP2 is a protein that in humans is encoded by the TARBP2 gene.

<span class="mw-page-title-main">TARBP1</span> Protein-coding gene in the species Homo sapiens

Probable methyltransferase TARBP1 is an enzyme that in humans is encoded by the TARBP1 gene.

Tat (HIV)

In molecular biology, Tat is a protein that is encoded for by the tat gene in HIV-1. Tat is a regulatory protein that drastically enhances the efficiency of viral transcription. Tat stands for "Trans-Activator of Transcription". The protein consists of between 86 and 101 amino acids depending on the subtype. Tat vastly increases the level of transcription of the HIV dsDNA. Before Tat is present, a small number of RNA transcripts will be made, which allow the Tat protein to be produced. Tat then binds to cellular factors and mediates their phosphorylation, resulting in increased transcription of all HIV genes, providing a positive feedback cycle. This in turn allows HIV to have an explosive response once a threshold amount of Tat is produced, a useful tool for defeating the body's response.

<span class="mw-page-title-main">Rev (HIV)</span> HIV-1 regulating protein

Rev is a transactivating protein that is essential to the regulation of HIV-1 protein expression. A nuclear localization signal is encoded in the rev gene, which allows the Rev protein to be localized to the nucleus, where it is involved in the export of unspliced and incompletely spliced mRNAs. In the absence of Rev, mRNAs of the HIV-1 late (structural) genes are retained in the nucleus, preventing their translation.

<span class="mw-page-title-main">Influenza virus pseudoknot</span>

The Influenza virus pseudoknot is an RNA pseudoknot structure formed in one of the non-structural coding segments (NS) of influenza virus genome. Pseudoknots are commonly found in viral genomes, especially RNA viruses, where they incorporate an RNA splice site and can have a wide range of functions. The orientation of the coaxially stacked stems in the influenza pseudoknot, however, differs from the most common topology in "classical" RNA pseudoknots.

<span class="mw-page-title-main">Complementarity (molecular biology)</span> Lock-and-key pairing between two structures

In molecular biology, complementarity describes a relationship between two structures each following the lock-and-key principle. In nature complementarity is the base principle of DNA replication and transcription as it is a property shared between two DNA or RNA sequences, such that when they are aligned antiparallel to each other, the nucleotide bases at each position in the sequences will be complementary, much like looking in the mirror and seeing the reverse of things. This complementary base pairing allows cells to copy information from one generation to another and even find and repair damage to the information stored in the sequences.

<span class="mw-page-title-main">Guanine tetrad</span> Structure in molecular biology

In molecular biology, a guanine tetrad is a structure composed of four guanine bases in a square planar array. They most prominently contribute to the structure of G-quadruplexes, where their hydrogen bonding stabilizes the structure. Usually, there are at least two guanine tetrads in a G-quadruplex, and they often feature Hoogsteen-style hydrogen bonding.

References

  1. Adapted from Proteopedia page.
  2. Forsdyke DR (September 1995). "A stem-loop "kissing" model for the initiation of recombination and the origin of introns". Molecular Biology and Evolution. 12 (5): 949–958. doi: 10.1093/oxfordjournals.molbev.a040273 . PMID   7476142.
  3. Nowakowski J, Tinoco Jr I (1997). "Semin". Virology. 8: 153–165. doi:10.1006/smvy.1997.0118.
  4. Kim CH, Tinoco I (August 2000). "A retroviral RNA kissing complex containing only two G.C base pairs". Proceedings of the National Academy of Sciences of the United States of America. 97 (17): 9396–9401. doi: 10.1073/pnas.170283697 . PMC   16875 . PMID   10931958.
  5. Andersen AA, Collins RA (July 2001). "Intramolecular secondary structure rearrangement by the kissing interaction of the Neurospora VS ribozyme". Proceedings of the National Academy of Sciences of the United States of America. 98 (14): 7730–7735. Bibcode:2001PNAS...98.7730A. doi: 10.1073/pnas.141039198 . PMC   35410 . PMID   11427714.
  6. Chen Y, Varani G (June 2010). "RNA Structure". Encyclopedia of Life Sciences. Chichester: John Wiley & Sons Ltd. doi:10.1002/9780470015902.a0001339.pub2. ISBN   978-0-470-01617-6.
  7. Chang KY, Tinoco I (August 1994). "Characterization of a "kissing" hairpin complex derived from the human immunodeficiency virus genome". Proceedings of the National Academy of Sciences of the United States of America. 91 (18): 8705–8709. Bibcode:1994PNAS...91.8705C. doi: 10.1073/pnas.91.18.8705 . PMC   44675 . PMID   8078946.
  8. Paillart JC, Westhof E, Ehresmann C, Ehresmann B, Marquet R (July 1997). "Non-canonical interactions in a kissing loop complex: the dimerization initiation site of HIV-1 genomic RNA". Journal of Molecular Biology. 270 (1): 36–49. doi:10.1006/jmbi.1997.1096. PMID   9231899.
  9. Paillart JC, Skripkin E, Ehresmann B, Ehresmann C, Marquet R (May 1996). "A loop-loop "kissing" complex is the essential part of the dimer linkage of genomic HIV-1 RNA". Proceedings of the National Academy of Sciences of the United States of America. 93 (11): 5572–5577. Bibcode:1996PNAS...93.5572P. doi: 10.1073/pnas.93.11.5572 . JSTOR   39474. PMC   39288 . PMID   8643617.

Further reading