Retrozyme

Last updated

Retrozymes are a family of retrotransposons first discovered in the genomes of plants [1] but now also known in genomes of animals. [2] Retrozymes contain a hammerhead ribozyme (HHR) in their sequences (and so the name retrozyme is a combination of retrotransposon and hammerhead ribozyme), although they do not possess any coding regions. Retrozymes are nonautonomous retroelements, and so borrow proteins from other elements to move into new regions of a genome. Retrozymes are actively transcribed into covalently closed circular RNAs (circRNAs or cccRNAs) and are detected in both polarities, which may indicate the use of rolling circle replication in their lifecycle. [3]

Contents

The genomic structure of a retrozyme in plants involves a central non-coding region that may stretch about 300–600nt flanked by long terminal repeats about 300–400nt containing the HHR motif. They also have two sequences (a primer binding site (PBS) complementary to the tRNA-Met sequence and a poly-purine tract (PPT)) needed to prime DNA synthesis during mobilization. The most distinguishing feature of the retrozyme compared with other elements of plant genomes are the hammerhead ribozyme. Otherwise, they resemble other known features of plant genomes such as terminal-repeat retrotransposons in miniature (TRIMs) and small LTR retrotransposons (SMARTs). The PBS, PPT, and the HHR motif are the only parts of the retrozyme sequences which shows conservation and homology. [4] Currently, it is thought retrozymes evolved from a large retrotransposon family known across many eukaryotes as the Penelope-like elements (PLEs). Retrozymes share a number of peculiar features with PLEs, including a type I HHR, occurrence as tandem copies, and co-existence in all analyzed metazoans to date. [2] [4]

Retrozymes are presently known to reach sequence sizes as small as 170nt and as big as 1,116nt. Smaller retrozymes are typically found in invertebrates, such as a 300nt retrozyme in the genome of the Mediterranean mussel (Mytilus galloprovincialis). The largest known retrozyme is 1,116nt in length, discovered in the genome of a strain of Jatropha curcas . [5]

Presently, the only database for retrozymes and similar elements is ViroidDB, which currently contains sequences of 73 retrozymes taken from the National Center for Biotechnology Information nucleotide database. [6] Sequences of retrozymes in particular were initially directly and separately found and downloaded from GenBank, as retrozymes currently have no taxonomic classification. [6] Some methods have been developed to study retrozymes in the laboratory. [7]

Traits

Retrozymes differentially accumulate in different tissues of plants. Furthermore, the domesticated equivalents of some species of plants contain substantially fewer copies of retrozymes, indicating that domestication applies a negative selection pressure on retrozyme sequences. Another interesting trait of retrozymes in plants is their active transcription, even though the majority of retrotransposons are inactive. [1]

The smallest known retrozymes are those found in invertebrates, where they can range from 170–400nt. They appear to be expressed in, at the least, most cell types. Just as with plants, retrozymes in animals are also expressed at high levels in both somatic cells and germ cells. While retrozymes have been found in both linear and circularized forms, levels of circularized retrozymes have been seen much more abundantly in vivo and the linear forms may be a product of self-cleavage by the HHR motif during replication or a result of spontaneous breakage during purification. [2]

Animal retrozymes have several differences with plant retrozymes. Different proteins circularize and reversibly transcribe plant and animal retrozymes during the replication cycle. Animal retrozymes lack all the characteristic long-terminal repeats, PBSs, and PPTs known in plant retrozymes. And while plant retrozymes only have one or two copies of the HHR motif, animal retrozymes may have many such copies. Animal retrozymes also have smaller tandem repeats that are often flanked by target side duplications (TSDs). TSDs in animals are typically 8–12bp, slightly larger than the 4bp TSDs found in plants. [8]

Replication cycle

The retrozyme sequence is first transcribed by a polymerase in the host. The product is an oligomeric RNA sequence which is a single transcript containing multiple copies of the retrozyme sequence. The hammerhead ribozyme motif then autocatalytically performs self-cleavage to separate the oligomeric transcript into several monomeric transcripts, each containing only one copy of the retrozyme sequence. This copy is an intermediate of the replication cycle, containing the opposite polarity of the original sequence with a 5'-hydroxyl and a 2'-3'-cyclic phosphate ends. A ligase protein in the host may then circularize this intermediate into a stable, circular RNA molecule. In plants, this ligase is a chloroplast tRNA ligase. Dependence on chloroplast tRNA ligase for circularization is also seen in the Avsunviroidae family of viroids. In animals, the ligase is an RtcB tRNA ligase. Reverse transcriptase activity is required from a different retrotransposon to generate a corresponding complementary DNA of the retrozyme RNA, and the polarity of this cDNA corresponds to the polarity of the original sequence. Plant and animal retrozymes rely on different retrotransposons to produce a cDNA copy of their RNA molecule. In plants, LTR retrotransposons of the Gypsy family are used. Although it is not clear which type of retrotransposons are relied on in animals, these could be classes such as LINEs or PLEs. After the DNA copy has been produced, the retrozyme sequence has the opportunity to re-insert itself into a genomic loci. [2]

Relationships with mobile genetic elements

Retrozymes possess close similarities to types of mobile genetic elements (MGE), especially viroids, satellite RNAs (satRNAs), and Ribozyviria (a recently described realm of viruses [9] ). For one, the hammerhead ribozyme (HHR) motif is found in all these elements. These elements also replicate through rolling circle replication, where the HHR motif plays the autocatalytic role of cleaving the circular RNA molecule at a conserved site. Furthermore, all these elements depend on a host polymerase to transcribe their sequence and a ligase to recircularize them into a circular RNA molecule. Retrozymes form branched conformations, as do some satRNAs and Avsunviroidae (one of the two classes of viroids). [3]

Due to their simplicity, many have suggested that viroids originated and are remnants of the RNA world. [10] [11] [12] Other suggestions include that viroids derive from other viruses, having degenerated in size and lost any protein-coding genes. Several challenges have been raised to these suggestions. The limited range of viroids and satellite RNAs in flowering plants (with none discovered in bacteria and archaea) indicates that their origins post-date the emergence of eukaryotes. [11] The recent discovery and advances related to retrozymes have led to the current hypothesis that retrozymes were the source of the origins of viroids and satRNAs. [13] The relationship with ribozyviruses is less straight forward. Ribozyviruses are more complex than retrozymes, viroids, and satellites. They are the only viroid-like element to harbour a protein-coding gene. This gene codes for a capsid which undergoes post-translational modifications to give rise to different forms which together perform a variety of functions in the host, enabling their lifecycle. Furthermore, ribozyviruses are only found narrowly in animal lineages whereas both viroids and satellite RNAs are only known to be infectious in plants. The narrow spread of ribozyviruses in animals, combined with strong evidence for the origins of viroids in plants, suggests that ribozyviruses are the more recent class of MGEs. Ribozyviruses may have emerged from viroids and then transferred into animals through horizontal gene transfer, at some point acquiring a protein-coding gene. Alternatively, because retrozymes are known in both plants and animals, retrozymes may have independently given rise to ribozyviruses in animal lineages. [3] It is unclear if viroids and other viroid-like elements emerged from retrozymes once or several times, and while they are unlikely to trace back to RNA world, some still stress their importance as minimal replicators close to the theoretical lower limit of replicator size. [3]

See also

Related Research Articles

<span class="mw-page-title-main">Genome</span> All genetic material of an organism

In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA. The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as regulatory sequences, and often a substantial fraction of junk DNA with no evident function. Almost all eukaryotes have mitochondria and a small mitochondrial genome. Algae and plants also contain chloroplasts with a chloroplast genome.

<span class="mw-page-title-main">Transposable element</span> Semiparasitic DNA sequence

A transposable element is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transposition often results in duplication of the same genetic material. In the human genome, L1 and Alu elements are two examples. Barbara McClintock's discovery of them earned her a Nobel Prize in 1983. Its importance in personalized medicine is becoming increasingly relevant, as well as gaining more attention in data analytics given the difficulty of analysis in very high dimensional spaces.

Viroids are small single-stranded, circular RNAs that are infectious pathogens. Unlike viruses, they have no protein coating. All known viroids are inhabitants of angiosperms, and most cause diseases, whose respective economic importance to humans varies widely. A recent metatranscriptomics study suggests that the host diversity of viroids and other viroid-like elements is broader than previously thought and that it would not be limited to plants, encompassing even the prokaryotes.

<span class="mw-page-title-main">Ribozyme</span> Type of RNA molecules

Ribozymes are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonstrated that RNA can be both genetic material and a biological catalyst, and contributed to the RNA world hypothesis, which suggests that RNA may have been important in the evolution of prebiotic self-replicating systems.

Virusoids are circular single-stranded RNA(s) dependent on viruses for replication and encapsidation. The genome of virusoids consist of several hundred (200–400) nucleotides and does not code for any proteins.

<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.

The Pospiviroidae are a incertae sedis family of ssRNA viroids with 5 genera and 39 species, including the first viroid to be discovered, PSTVd, which is part of genus Pospiviroid. Their secondary structure is key to their biological activity. The classification of this family is based on differences in the conserved central region sequence. Pospiviroidae replication occurs in an asymmetric fashion via host cell RNA polymerase, RNase, and RNA ligase. its hosts are plants, specifically dicotyledons and some monocotyledons

<span class="mw-page-title-main">Rolling circle replication</span> DNA synthesis technique

Rolling circle replication (RCR) is a process of unidirectional nucleic acid replication that can rapidly synthesize multiple copies of circular molecules of DNA or RNA, such as plasmids, the genomes of bacteriophages, and the circular RNA genome of viroids. Some eukaryotic viruses also replicate their DNA or RNA via the rolling circle mechanism.

<span class="mw-page-title-main">Non-cellular life</span> Life that has no cellular structure

Non-cellular life, also known as acellular life, is life that exists without a cellular structure for at least part of its life cycle. Historically, most definitions of life postulated that an organism must be composed of one or more cells, but this is for some no longer considered necessary, and modern criteria allow for forms of life based on other structural arrangements.

Exon shuffling is a molecular mechanism for the formation of new genes. It is a process through which two or more exons from different genes can be brought together ectopically, or the same exon can be duplicated, to create a new exon-intron structure. There are different mechanisms through which exon shuffling occurs: transposon mediated exon shuffling, crossover during sexual recombination of parental genomes and illegitimate recombination.

<span class="mw-page-title-main">Mobile genetic elements</span> DNA sequence whose position in the genome is variable

Mobile genetic elements (MGEs) sometimes called selfish genetic elements are a type of genetic material that can move around within a genome, or that can be transferred from one species or replicon to another. MGEs are found in all organisms. In humans, approximately 50% of the genome is thought to be MGEs. MGEs play a distinct role in evolution. Gene duplication events can also happen through the mechanism of MGEs. MGEs can also cause mutations in protein coding regions, which alters the protein functions. These mechanisms can also rearrange genes in the host genome generating variation. These mechanism can increase fitness by gaining new or additional functions. An example of MGEs in evolutionary context are that virulence factors and antibiotic resistance genes of MGEs can be transported to share genetic code with neighboring bacteria. However, MGEs can also decrease fitness by introducing disease-causing alleles or mutations. The set of MGEs in an organism is called a mobilome, which is composed of a large number of plasmids, transposons and viruses.

<i>Avsunviroidae</i> Family of viruses

The Avsunviroidae are a family of viroids. There are four species in three genera. They consist of RNA genomes between 246 and 375 nucleotides in length. They are single-stranded covalent circles and have intramolecular base pairing. All members lack a central conserved region.

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

The hammerhead ribozyme is an RNA motif that catalyzes reversible cleavage and ligation reactions at a specific site within an RNA molecule. It is one of several catalytic RNAs (ribozymes) known to occur in nature. It serves as a model system for research on the structure and properties of RNA, and is used for targeted RNA cleavage experiments, some with proposed therapeutic applications. Named for the resemblance of early secondary structure diagrams to a hammerhead shark, hammerhead ribozymes were originally discovered in two classes of plant virus-like RNAs: satellite RNAs and viroids. They are also known in some classes of retrotransposons, including the retrozymes. The hammerhead ribozyme motif has been ubiquitously reported in lineages across the tree of life.

<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">Hepatitis delta virus ribozyme</span>

The hepatitis delta virus (HDV) ribozyme is a non-coding RNA found in the hepatitis delta virus that is necessary for viral replication and is the only known human virus that utilizes ribozyme activity to infect its host. The ribozyme acts to process the RNA transcripts to unit lengths in a self-cleavage reaction during replication of the hepatitis delta virus, which is thought to propagate by a double rolling circle mechanism. The ribozyme is active in vivo in the absence of any protein factors and was the fastest known naturally occurring self-cleaving RNA at the time of its discovery.

<span class="mw-page-title-main">R2 RNA element</span>

The R2 RNA element is a non-long terminal repeat (non-LTR) retrotransposable element that inserts at a specific site in the 28S ribosomal RNA (rRNA) genes of most insect genomes. In order to insert itself into the genome, retrotransposon encoded protein (R2) protein makes a specific nick in one of the DNA strands at the insertion site and uses the 3′ hydroxyl group exposed by this nick to prime the reverse transcription process termed target primed reverse transcription (TPRT), where the RNA genome is transcribed into DNA.

<span class="mw-page-title-main">Circular RNA</span> Type of RNA found in cells

Circular RNA is a type of single-stranded RNA which, unlike linear RNA, forms a covalently closed continuous loop. In circular RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together. This feature confers numerous properties to circular RNA, many of which have only recently been identified.

<span class="mw-page-title-main">Long interspersed nuclear element</span>

Long interspersed nuclear elements (LINEs) are a group of non-LTR retrotransposons that are widespread in the genome of many eukaryotes. LINEs contain an internal Pol II promoter to initiate transcription into mRNA, and encode one or two proteins, ORF1 and ORF2. The functional domains present within ORF1 vary greatly among LINEs, but often exhibit RNA/DNA binding activity. ORF2 is essential to successful retrotransposition, and encodes a protein with both reverse transcriptase and endonuclease activity.

<span class="mw-page-title-main">Short interspersed nuclear element</span>

Short interspersed nuclear elements (SINEs) are non-autonomous, non-coding transposable elements (TEs) that are about 100 to 700 base pairs in length. They are a class of retrotransposons, DNA elements that amplify themselves throughout eukaryotic genomes, often through RNA intermediates. SINEs compose about 13% of the mammalian genome.

<span class="mw-page-title-main">Ribozyviria</span> Realm of viruses

Ribozyviria is a realm of satellite nucleic acids — infectious agents that resemble viruses, but cannot replicate without a helper virus. Established in ICTV TaxoProp 2020.012D, the realm is named after the presence of genomic and antigenomic ribozymes of the Deltavirus type. The agents in Ribozyviria are satellite nucleic acids, which are distinct from satellite viruses in that they do not encode all of their own structural proteins but require proteins from their helper viruses in order to assemble. Additional common features include a rod-like structure, an RNA-binding "delta antigen" encoded in the genome, and animal hosts. Furthermore, the size range of the genomes of these viruses is between around 1547–1735nt, they encode a hammerhead ribozyme or a hepatitis delta virus ribozyme, and their coding capacity only involves one conserved protein. Most lineages of this realm are poorly understood, the notable exception being the genus Deltavirus, comprising the causal agents of hepatitis D in humans.

References

  1. 1 2 Cervera, Amelia; Urbina, Denisse; de la Peña, Marcos (2016-06-23). "Retrozymes are a unique family of non-autonomous retrotransposons with hammerhead ribozymes that propagate in plants through circular RNAs". Genome Biology. 17 (1): 135. doi: 10.1186/s13059-016-1002-4 . ISSN   1474-760X. PMC   4918200 . PMID   27339130.
  2. 1 2 3 4 Cervera, Amelia; Peña, Marcos (2020-05-21). "Small circRNAs with self-cleaving ribozymes are highly expressed in diverse metazoan transcriptomes". Nucleic Acids Research. 48 (9): 5054–5064. doi:10.1093/nar/gkaa187. ISSN   0305-1048. PMC   7229834 . PMID   32198887.
  3. 1 2 3 4 Lee, Benjamin D.; Koonin, Eugene V. (2022-01-12). "Viroids and Viroid-like Circular RNAs: Do They Descend from Primordial Replicators?". Life. 12 (1): 103. doi: 10.3390/life12010103 . ISSN   2075-1729. PMC   8781251 . PMID   35054497.
  4. 1 2 de la Peña, Marcos; Cervera, Amelia (2017-08-03). "Circular RNAs with hammerhead ribozymes encoded in eukaryotic genomes: The enemy at home". RNA Biology. 14 (8): 985–991. doi:10.1080/15476286.2017.1321730. ISSN   1547-6286. PMC   5680766 . PMID   28448743.
  5. ↑ "ViroidDB". viroids.org. Retrieved 2022-01-20.
  6. 1 2 Lee, Benjamin D; Neri, Uri; Oh, Caleb J; Simmonds, Peter; Koonin, Eugene V (2022-01-07). "ViroidDB: a database of viroids and viroid-like circular RNAs". Nucleic Acids Research. 50 (D1): D432–D438. doi:10.1093/nar/gkab974. ISSN   0305-1048. PMC   8728161 . PMID   34751403.
  7. ↑ Cervera, Amelia; de la Peña, Marcos (2021), Scarborough, Robert J; Gatignol, Anne (eds.), "Cloning and Detection of Genomic Retrozymes and Their circRNA Intermediates", Ribozymes, Methods in Molecular Biology, New York, NY: Springer US, vol. 2167, pp. 27–44, doi:10.1007/978-1-0716-0716-9_3, ISBN   978-1-0716-0715-2, PMID   32712913, S2CID   220797209 , retrieved 2022-01-20
  8. ↑ de la Peña, Marcos (2018), Xiao, Junjie (ed.), "Circular RNAs Biogenesis in Eukaryotes Through Self-Cleaving Hammerhead Ribozymes" , Circular RNAs: Biogenesis and Functions, Advances in Experimental Medicine and Biology, Singapore: Springer, vol. 1087, pp. 53–63, doi:10.1007/978-981-13-1426-1_5, ISBN   978-981-13-1426-1, PMID   30259357 , retrieved 2022-01-20
  9. ↑ Hepojoki, Jussi; Hetzel, Udo; Paraskevopoulou, Sofia; Drosten, Christian; Balazs Harrach; Zerbini, Francisco Murilo; Koonin, Eugene V; Krupovic, Mart; Dolja, Valerian V.; Kuhn, Jens H. (2021). "Create one new realm (Ribozyviria) including one new family (Kolmioviridae) including genus Deltavirus and seven new genera for a total of 15 species". doi:10.13140/RG.2.2.31235.43041.{{cite journal}}: Cite journal requires |journal= (help)
  10. ↑ Diener, T. O. (1989-12-01). "Circular RNAs: relics of precellular evolution?". Proceedings of the National Academy of Sciences. 86 (23): 9370–9374. Bibcode:1989PNAS...86.9370D. doi: 10.1073/pnas.86.23.9370 . ISSN   0027-8424. PMC   298497 . PMID   2480600.
  11. 1 2 Diener, Theodor O. (2016). "Viroids: "living fossils" of primordial RNAs?". Biology Direct. 11 (1): 15. doi: 10.1186/s13062-016-0116-7 . ISSN   1745-6150. PMC   4807594 . PMID   27016066.
  12. ↑ Moelling, Karin; Broecker, Felix (2021-03-28). "Viroids and the Origin of Life". International Journal of Molecular Sciences. 22 (7): 3476. doi: 10.3390/ijms22073476 . ISSN   1422-0067. PMC   8036462 . PMID   33800543.
  13. ↑ de la Peña, Marcos; Cervera, Amelia (2017-08-03). "Circular RNAs with hammerhead ribozymes encoded in eukaryotic genomes: The enemy at home". RNA Biology. 14 (8): 985–991. doi:10.1080/15476286.2017.1321730. ISSN   1547-6286. PMC   5680766 . PMID   28448743.
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.