Retrozymes are a family of
retrotransposon
Retrotransposons (also called Class I transposable elements or transposons via RNA intermediates) are a type of genetic component that copy and paste themselves into different genomic locations (transposon) by converting RNA back into DNA through ...
s first discovered in the genomes of
plant
Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...
s
but now also known in genomes of
animal
Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...
s.
Retrozymes contain a
hammerhead ribozyme
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 ...
(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
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s from other elements to move into new regions of a
genome
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 (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
. 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
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 genom ...
in their lifecycle.
The genomic structure of a retrozyme in plants involves a central
non-coding region
Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, microRNA, piRNA, ribosomal RNA, and regula ...
that may stretch about 300–600nt flanked by
long terminal repeat
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 ...
s about 300–400nt containing the HHR motif. They also have two sequences (a
primer binding site A primer binding site is a region of a nucleotide sequence where an RNA or DNA single-stranded primer binds to start replication. The primer binding site is on one of the two complementary strands of a double-stranded nucleotide polymer, in the ...
(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
Homology may refer to:
Sciences
Biology
*Homology (biology), any characteristic of biological organisms that is derived from a common ancestor
* Sequence homology, biological homology between DNA, RNA, or protein sequences
*Homologous chrom ...
.
Currently, it is thought retrozymes evolved from a large retrotransposon family known across many
eukaryotes
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
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.
Retrozymes are presently known to reach sequence sizes as small as 170nt and as big as 1,116nt. Smaller retrozymes are typically found in
invertebrate
Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...
s, such as a 300nt retrozyme in the genome of the
Mediterranean mussel
The Mediterranean mussel (''Mytilus galloprovincialis'') is a species of bivalve, a marine (ocean), marine mollusc in the family (biology), family Mytilidae. It is an invasive species in many parts of the world, and also an object of aquaculture ...
(''Mytilus galloprovincialis''). The largest known retrozyme is 1,116nt in length, discovered in the genome of a strain of ''
Jatropha curcas
''Jatropha curcas'' is a species of flowering plant in the spurge family, Euphorbiaceae, that is native to the American tropics, most likely Mexico and Central America. It is originally native to the tropical areas of the Americas from Mexico to ...
''.
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
The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The ...
nucleotide database.
Sequences of retrozymes in particular were initially directly and separately found and downloaded from
GenBank
The GenBank sequence database is an open access, annotated collection of all publicly available nucleotide sequences and their protein translations. It is produced and maintained by the National Center for Biotechnology Information (NCBI; a part ...
, as retrozymes currently have no taxonomic classification.
Some methods have been developed to study retrozymes in the laboratory.
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
Domestication is a sustained multi-generational relationship in which humans assume a significant degree of control over the reproduction and care of another group of organisms to secure a more predictable supply of resources from that group. ...
applies a
negative selection pressure on retrozyme sequences. Another interesting trait of retrozymes in plants is their active transcription, even though the majority of
retrotransposon
Retrotransposons (also called Class I transposable elements or transposons via RNA intermediates) are a type of genetic component that copy and paste themselves into different genomic locations (transposon) by converting RNA back into DNA through ...
s are inactive.
The smallest known retrozymes are those found in
invertebrate
Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...
s, 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 cell
A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells compo ...
s and
germ cell
Germ or germs may refer to:
Science
* Germ (microorganism), an informal word for a pathogen
* Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually
* Germ layer, a primary layer of cells that forms during embry ...
s. 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.
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.
Replication cycle
The retrozyme sequence is first transcribed by a
polymerase
A polymerase is an enzyme ( EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using base- ...
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
In biochemistry, a ligase is an enzyme that can catalyze the joining (ligation) of two large molecules by forming a new chemical bond. This is typically via hydrolysis of a small pendant chemical group on one of the larger molecules or the enzym ...
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
The ''Avsunviroidae'' are a family of viroids. There are four species in three genera (''Avsunviroid'', ''Elaviroid'' and ''Pelamoviroid''). They consist of RNA genomes between 246 and 375 nucleotides in length. They are single-stranded covalent ...
'' family of
viroid
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 (flowering plants), and most cause diseases, whose respective economi ...
s. In animals, the ligase is an RtcB tRNA ligase.
Reverse transcriptase
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, ...
activity is required from a different
retrotransposon
Retrotransposons (also called Class I transposable elements or transposons via RNA intermediates) are a type of genetic component that copy and paste themselves into different genomic locations (transposon) by converting RNA back into DNA through ...
to generate a corresponding
complementary DNA
In genetics, complementary DNA (cDNA) is DNA synthesized from a single-stranded RNA (e.g., messenger RNA (mRNA) or microRNA (miRNA)) template in a reaction catalyzed by the enzyme reverse transcriptase. cDNA is often used to express a spe ...
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.
Relationships with mobile genetic elements
Retrozymes possess close similarities to types of
mobile genetic elements
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 h ...
(MGE), especially
viroid
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 (flowering plants), and most cause diseases, whose respective economi ...
s,
satellite RNAs (satRNAs), and
Ribozyviria
''Ribozyviria'' is a realm of satellite nucleic acids. Established in ICTV TaxoProp 2020.012D, the realm is named after the presence of genomic and antigenomic ribozymes of the ''Deltavirus'' type. Additional common features include a rod-like s ...
(a recently described
realm
A realm is a community or territory over which a sovereign rules. The term is commonly used to describe a monarchical or dynastic state. A realm may also be a subdivision within an empire, if it has its own monarch, e.g. the German Empire.
Etym ...
of
virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
es). For one, the hammerhead ribozyme (HHR) motif is found in all these elements. These elements also replicate through
rolling circle replication
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 genom ...
, where the HHR motif plays the
autocatalytic
A single chemical reaction is said to be autocatalytic if one of the reaction products is also a catalyst for the same or a coupled reaction.Steinfeld J.I., Francisco J.S. and Hase W.L. ''Chemical Kinetics and Dynamics'' (2nd ed., Prentice-Hall 199 ...
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
The ''Avsunviroidae'' are a family of viroids. There are four species in three genera (''Avsunviroid'', ''Elaviroid'' and ''Pelamoviroid''). They consist of RNA genomes between 246 and 375 nucleotides in length. They are single-stranded covalent ...
'' (one of the two classes of viroids).
Due to their simplicity, many have suggested that viroids originated and are remnants of the
RNA world
The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence ...
.
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
Flowering plants are plants that bear flowers and fruits, and form the clade Angiospermae (), commonly called angiosperms. The term "angiosperm" is derived from the Greek words ('container, vessel') and ('seed'), and refers to those plants th ...
(with none discovered in
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
and
archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
) indicates that their origins post-date the emergence of
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s.
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.
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
A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...
which undergoes
post-translational modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosome ...
s 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
Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between Unicellular organism, unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offsprin ...
, 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.
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.
See also
*
Hammerhead ribozyme
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 ...
*
Retrotransposon
Retrotransposons (also called Class I transposable elements or transposons via RNA intermediates) are a type of genetic component that copy and paste themselves into different genomic locations (transposon) by converting RNA back into DNA through ...
*
Ribozyviria
''Ribozyviria'' is a realm of satellite nucleic acids. Established in ICTV TaxoProp 2020.012D, the realm is named after the presence of genomic and antigenomic ribozymes of the ''Deltavirus'' type. Additional common features include a rod-like s ...
*
Satellite (biology)
A satellite is a subviral agent that depends on the coinfection of a host cell with a helper virus for its replication. Satellites can be divided into two major classes: satellite viruses and satellite nucleic acids. Satellite viruses, which ar ...
*
Viroid
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 (flowering plants), and most cause diseases, whose respective economi ...
*
Virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
References
External links
ViroidDB a database of viroid and viroid-like circular RNAs
{{Organisms et al.
Mobile genetic elements