Retron Organization
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A retron is a distinct DNA sequence found in the
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 ...
of many
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 ...
species that codes for
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, ...
and a unique single-stranded DNA/RNA hybrid called
multicopy single-stranded DNA 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 ch ...
(msDNA). Retron msr RNA is the
non-coding RNA A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-c ...
produced by retron elements and is the immediate precursor to the synthesis of msDNA. The retron msr RNA folds into a characteristic secondary structure that contains a conserved
guanosine Guanosine (symbol G or Guo) is a purine nucleoside comprising guanine attached to a ribose (ribofuranose) ring via a β-N9-glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate (GMP), cyclic guanosine monophosphate (c ...
residue at the end of a stem loop. Synthesis of DNA by the retron-encoded reverse transcriptase (RT) results in a DNA/RNA chimera which is composed of small single-stranded DNA linked to small single-stranded RNA. The RNA strand is joined to the
5′ Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. In a single strand of DNA or RNA, the chemical convention of naming carbon atoms in the nucleotide pentose-sugar-ri ...
end of the DNA chain via a 2′–5′ phosphodiester linkage that occurs from the 2′ position of the conserved internal guanosine residue.


Sequence and structure

Retron elements are about 2 kb long. They contain a single
operon In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...
controlling the synthesis of an RNA transcript carrying three loci, ''msr'', ''msd'', and ''ret'', that are involved in msDNA synthesis. The DNA portion of msDNA is encoded by the ''msd'' gene, the RNA portion is encoded by the ''msr'' gene, while the product of the ''ret'' gene is a reverse transcriptase similar to the RTs produced by
retrovirus 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. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase ...
es and other types of retroelements. Like other reverse transcriptases, the retron RT contains seven regions of conserved
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s (labeled 1–7 in the figure), including a highly conserved tyr-
ala Ala, ALA, Alaa or Alae may refer to: Places * Ala, Hiiu County, Estonia, a village * Ala, Valga County, Estonia, a village * Ala, Alappuzha, Kerala, India, a village * Ala, Iran, a village in Semnan Province * Ala, Gotland, Sweden * Alad, S ...
- asp- asp (YADD) sequence associated with the catalytic core. The ''ret'' gene product is responsible for processing the ''msd/msr'' portion of the RNA transcript into msDNA.


Classification and occurrence

For many years after their discovery in animal viruses, reverse transcriptases were believed to be absent from
prokaryote A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
s. Currently, however, RT-encoding elements, ''i.e.''
retroelement 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, have been found in a wide variety of different bacteria: *Retrons were the first family of retroelement discovered in bacteria; the other two families of known bacterial retroelements are: *
group II intron Group II introns are a large class of self-catalytic ribozymes and mobile genetic elements found within the genes of all three domains of life. Ribozyme activity (e.g., self- splicing) can occur under high-salt conditions ''in vitro''. However, ...
s: Group II introns are the best characterized bacterial retroelement and the only type known to exhibit autonomous mobility; they consist of an RT encoded within a catalytic, self-splicing RNA structure. Group II intron mobility is mediated by a
ribonucleoprotein Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins. Structures Nucleoproteins tend to be positively charged, facilitating in ...
comprising an intron lariat bound to two intron-coded proteins. * diversity-generating retroelements (DGRs). The DGRs are not mobile, but function to diversify DNA sequences. For example, DGRs mediate the switch between pathogenic and free-living phases of ''
Bordetella ''Bordetella'' () is a genus of small (0.2 – 0.7 µm), gram-negative coccobacilli of the phylum Pseudomonadota. ''Bordetella'' species, with the exception of '' B. petrii'', are obligate aerobes, as well as highly fastidious, or difficult ...
.''


Function

Since retrons are not mobile, their appearance in diverse bacterial species is not a "
selfish DNA Selfish genetic elements (historically also referred to as selfish genes, ultra-selfish genes, selfish DNA, parasitic DNA and genomic outlaws) are genetic segments that can enhance their own transmission at the expense of other genes in the genome, ...
" phenomenon. Rather, bacterial retrons confer some protection from phage infection to bacterial hosts. Several retrons are located in DNA regions next to certain protein effector-coding genes. When their expression is activated, most of these effectors and their associated retrons function together to block phage infection. Retrons are being developed into genome-editing tools.


References


External links

*
Mystery molecule in bacteria is revealed to be a guard
on: EurekAlert!, 5 Nov 2020. Source: WEIZMANN INSTITUTE OF SCIENCE {{Organisms et al. Non-coding RNA