Coronavirus 3′ stem-loop II-like motif (s2m)

{{Infobox rfam

| Name = Coronavirus 3′ stem-loop II-like motif (s2m)

| image = RF00164-rscape.svg

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| caption = Predicted secondary structure and sequence conservation of s2m

| Symbol = s2m

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| Rfam = RF00164

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| RNA_type = Cis-reg

| Tax_domain = Eukaryota; Viruses

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| SO = {{SO|0000233}}

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The Coronavirus 3′ stem-loop II-like motif (also known as s2m) is a secondary structure motif identified in the 3′ untranslated region (3′UTR) of astrovirus, coronavirus and equine rhinovirus genomes.{{cite journal | vauthors = Jonassen CM, Jonassen TO, Grinde B | title = A common RNA motif in the 3' end of the genomes of astroviruses, avian infectious bronchitis virus and an equine rhinovirus | journal = The Journal of General Virology | volume = 79 ( Pt 4) | issue = 4 | pages = 715–8 | date = April 1998 | pmid = 9568965 | doi = 10.1099/0022-1317-79-4-715 | doi-access = free }} Its function is unknown, but various viral 3′ UTR regions have been found to play roles in viral replication and packaging.

This motif appears to be conserved in both nucleotide sequence and secondary structure folding indicating a strong evolutionary selection for its conservation. The presence of this conserved motif in different viral families is suggested to be the result of at least two separate recombination events. To date s2m has been described in four families of positive sense single-stranded RNA viruses; Astroviridae, Caliciviridae, Picornaviridae and Coronaviridae. The viruses that contain s2m can infect a wide range of higher vertebrates, including birds, bats, horses, dogs and humans, and display different tissue tropisms.{{cite journal | vauthors = Tengs T, Kristoffersen AB, Bachvaroff TR, Jonassen CM | title = A mobile genetic element with unknown function found in distantly related viruses | journal = Virology Journal | volume = 10 | issue = 1 | pages = 132 | date = April 2013 | pmid = 23618040 | pmc = 3653767 | doi = 10.1186/1743-422X-10-132 | doi-access = free }}{{cite journal | vauthors = Rangan R, Zheludev IN, Hagey RJ, et al. | title = RNA genome conservation and secondary structure in SARS-CoV-2 and SARS-related viruses: a first look | journal = RNA | volume = 26 | issue = 8 | pages = 937–959 | date = August 2020 | pmid = 32398273 | doi = 10.1261/rna.076141.120 | pmc = 7373990 }} There seems to be a xenologue of s2m in a number of only distantly related insect species.{{cite journal | vauthors = Tengs T, Delwiche CF, Monceyron Jonassen C | title = A genetic element in the SARS-CoV-2 genome is shared with multiple insect species | journal = The Journal of General Virology | volume = 102 | issue = 3 | date = March 2021 | pmid = 33427605 | doi = 10.1099/jgv.0.001551|pmc=8515862 | doi-access = free }}

Other RNA families identified in the coronavirus include the coronavirus frameshifting stimulation element, the coronavirus packaging signal and the coronavirus 3′ UTR pseudoknot.

File:PDB_1xjr_EBI.png

Biological significance

Functionally during host invasion by viral RNA, it appears that s2m first binds one or more proteins as a mechanism for the viral RNA to substitute host protein synthesis. This has also been seen in s2m RNA macromolecular substitution of ribosomal RNA folds. The s2m RNA element are also effective targets for the design of anti-viral drugs and antisense oligonucleotides.{{cite journal | vauthors = Lulla V, Wandel MP, Bandyra KJ, et al. | title = Targeting the Conserved Stem Loop 2 Motif in the SARS-CoV-2 Genome | journal = J Virol | volume = 95 | issue = 14 | pages = e0066321 | date = June 2021 | pmid = 33963053 | doi = 10.1128/JVI.00663-21 |pmc=8223950 }} File:S2m structure of SARS-CoV.png Potential interacting human microRNA targets of SARS-CoV-2 that share similarity with those of influenza A virus H1N1 was identified as therapeutic targets.{{cite journal | vauthors = Chan AP, Choi Y, Schork NJ | title = Conserved genomic terminals OF SARS-COV-2 as co-evolving functional elements and potential therapeutic targets | journal = mSphere | volume = 5 | issue = 6 | pages = e00754-20 | date = November 2020 | pmid = 33239366 | doi = 10.1128/mSphere.00754-20 | pmc = 7690956 }}

Different structure between SARS-CoV-1 and SARS-CoV-2 s2m

The overall X-ray (2.7-Å) crystal structure of the s2m SARS-CoV-1 RNA and is different from the SARS-CoV-2 s2m secondary structure determined by NMR.{{cite journal | vauthors = Rangan R, Watkins AM, Chacon J, et al. | title = De novo 3D models of SARS-CoV-2 RNA elements from consensus experimental secondary structures | journal = Nucleic Acids Res. | volume = 49 | issue = 6 | pages = 3092–3108 | date = March 2021 | pmid = 33693814 | doi = 10.1093/nar/gkab119 | pmc = 8034642 }} Long-distance interactions between the 5′ UTR and s2m in SARS-CoV-2 genomic RNA have been suggested.{{cite journal | vauthors = Ziv O, Price J, Shalamova L, et al. | title = The Short- and Long-Range RNA-RNA Interactome of SARS-CoV-2 | journal = Molecular Cell | volume = 80 | issue = 6 | pages = 1067–1077 | date = December 2020 | pmid = 33259809 | doi = 10.1016/j.molcel.2020.11.004| pmc = 7643667 }}

Mutations of SARS-CoV-2 s2m: recombination hotspots rather than a conserved RNA motif

During COVID-19 pandemic in 2020, many genomic sequences of Australian SARS‐CoV‐2 isolates have deletions or mutations (29742G>A or 29742G>U; "G19A" or "G19U") in the s2m, suggesting that RNA recombination may have occurred in this RNA element. 29742G("G19"), 29744G("G21"), and 29751G("G28") were predicted as recombination hotspots.{{cite journal | vauthors = Yeh TY, Contreras GP | title = Emerging viral mutants in Australia suggest RNA recombination event in the SARS-CoV-2 genome | journal = The Medical Journal of Australia | volume = 213 | issue = 1 | pages = 44–44.e1 | date = July 2020 | pmid = 32506536 | pmc = 7300921 | doi = 10.5694/mja2.50657 }} 29742G>U mutation was also linked to travellers returning from Iran to Australia and New Zealand.{{cite journal | vauthors = Eden JS, Rockett R, Carter I et al. | title = An emergent clade of SARS-CoV-2 linked to returned travellers from Iran | journal = Virus Evolution | volume = 6 | issue = 1 | pages = veaa027 | date = April 2020 | pmid = 32296544 | pmc = 7147362 | doi = 10.1093/ve/veaa027}} In three patients in Diamond Princess cruise, two mutations, 29736G > T and 29751G > T ("G13" and "G28") were found in s2m of SARS-CoV-2, as "G28" was predicted as recombination hotspots in Australian SARS-CoV-2 mutants. This result suggests that s2m of SARS-CoV-2 is RNA recombination/mutation hotspot rather than a conserved RNA motif found in other coronaviruses.{{cite journal | vauthors = Yeh TY, Contreras GP | title = Viral transmission and evolution dynamics of SARS-CoV-2 in shipboard quarantine | journal = Bull. World Health Organ. | volume = 99 | issue = 7 | pages = 486–495| date = 1 July 2021 | doi = 10.2471/BLT.20.255752 | pmid = 34248221 | pmc = 8243027 }}

Molecular dynamics simulations shows that both S2M variants, 29734G>C (G11C) and 29742G>U (G19U), of SARS-CoV-2 change RNA structure stability, raising questions as to the functional relevance of s2m in SARS-CoV-2 replication.{{cite journal | vauthors = Ryder SP, Morgan BR, Coskun P, et al. | title = Analysis of Emerging Variants in Structured Regions of the SARS-CoV-2 Genome | journal = Evol Bioinform Online | volume = 17 | pages = 11769343211014167 | date = May 2021 | pmid = 34017166 | doi = 10.1177/11769343211014167 |pmc=8114311 }}

References

External links

{{Rfam|id=RF00164|name=Coronavirus 3′ stem-loop II-like motif (s2m)}}
[https://web.archive.org/web/20060819210716/http://athena.bioc.uvic.ca/sars/map/s2mmotif_main.html S2M motif]

Category:Cis-regulatory RNA elements