scholarly journals RNA genome conservation and secondary structure in SARS-CoV-2 and SARS-related viruses

Author(s):  
Ramya Rangan ◽  
Ivan N. Zheludev ◽  
Rhiju Das

AbstractAs the COVID-19 outbreak spreads, there is a growing need for a compilation of conserved RNA genome regions in the SARS-CoV-2 virus along with their structural propensities to guide development of antivirals and diagnostics. Using sequence alignments spanning a range of betacoronaviruses, we rank genomic regions by RNA sequence conservation, identifying 79 regions of length at least 15 nucleotides as exactly conserved over SARS-related complete genome sequences available near the beginning of the COVID-19 outbreak. We then confirm the conservation of the majority of these genome regions across 739 SARS-CoV-2 sequences reported to date from the current COVID-19 outbreak, and we present a curated list of 30 ‘SARS-related-conserved’ regions. We find that known RNA structured elements curated as Rfam families and in prior literature are enriched in these conserved genome regions, and we predict additional conserved, stable secondary structures across the viral genome. We provide 106 ‘SARS-CoV-2-conserved-structured’ regions as potential targets for antivirals that bind to structured RNA. We further provide detailed secondary structure models for the 5’ UTR, frame-shifting element, and 3’ UTR. Last, we predict regions of the SARS-CoV-2 viral genome have low propensity for RNA secondary structure and are conserved within SARS-CoV-2 strains. These 59 ‘SARS-CoV-2-conserved-unstructured’ genomic regions may be most easily targeted in primer-based diagnostic and oligonucleotide-based therapeutic strategies.

2021 ◽  
Author(s):  
Marta Soszynska-Jozwiak ◽  
Ryszard Kierzek ◽  
Elzbieta Kierzek

SARS-CoV-2 belongs the Coronavirinae family. As other coronaviruses, SARS-CoV-2 is enveloped and possesses positive-sense, single-stranded RNA genome of ~30 kb. Genome RNA is used as the template for replication and transcription. During these processes, positive-sense genomic RNA (gRNA) and subgenomic RNAs (sgRNAs) are created. Several studies showed importance of genomic RNA secondary structure in SARS-CoV-2 replication. However, the structure of sgRNAs have remained largely unsolved so far. In this study, we performed probing of sgRNA M of SARS-CoV-2 in vitro. This is the first experimentally informed secondary structure model of sgRNA M, which presents features likely to be important in sgRNA M function. The knowledge about sgRNA M provides insights to better understand virus biology and could be used for designing new therapeutics.


2013 ◽  
Vol 11 (06) ◽  
pp. 1343002 ◽  
Author(s):  
YUTA TANIGUCHI ◽  
YASUHIRO YAMADA ◽  
OSAMU MARUYAMA ◽  
SATORU KUHARA ◽  
DAISUKE IKEDA

Sequence analysis is important to understand a genome, and a number of approaches such as sequence alignments and hidden Markov models have been employed. In the field of text mining, the purity measure is developed to detect unusual regions of a string without any domain knowledge. It is reported in that work that only RNAs and transposons are shown to have high purity values. In this work, the purity values of regions of various bacterial genome sequences are computed, and those regions are analyzed extensively. It is found that mobile elements and phages as well as RNAs and transposons have high purity values. It is interesting that they are all classified into a group of horizontally transferred genes. This means that the purity measure is useful to predict horizontally transferred genes.


1998 ◽  
Vol 72 (10) ◽  
pp. 7926-7933 ◽  
Author(s):  
John F. Repass ◽  
Shinji Makino

ABSTRACT The RNA elements that are required for replication of defective interfering (DI) RNA of the JHM strain of mouse hepatitis virus (MHV) consist of three discontinuous genomic regions: about 0.46 to 0.47 kb from both terminal sequences and an internal 58-nucleotide (nt)-long sequence (58-nt region) present at about 0.9 kb from the 5′ end of the DI genome. The internal region is important for positive-strand DI RNA synthesis (Y. N. Kim and S. Makino, J. Virol. 69:4963–4971, 1995). We further characterized the 58-nt region in the present study and obtained the following results. (i) The positive-strand RNA structure in solution was comparable with that predicted by computer modeling. (ii) Positive-strand RNA secondary structure, but not negative-strand RNA structure, was important for the biological function of the region. (iii) The biological function had a sequence-specific requirement. We discuss possible mechanisms by which the internal cis-acting signal drives MHV positive-strand DI RNA synthesis.


Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1555
Author(s):  
Simón Poblete ◽  
Horacio V. Guzman

Three-dimensional RNA domain reconstruction is important for the assembly, disassembly and delivery functionalities of a packed proteinaceus capsid. However, to date, the self-association of RNA molecules is still an open problem. Recent chemical probing reports provide, with high reliability, the secondary structure of diverse RNA ensembles, such as those of viral genomes. Here, we present a method for reconstructing the complete 3D structure of RNA genomes, which combines a coarse-grained model with a subdomain composition scheme to obtain the entire genome inside proteinaceus capsids based on secondary structures from experimental techniques. Despite the amount of sampling involved in the folded and also unfolded RNA molecules, advanced microscope techniques can provide points of anchoring, which enhance our model to include interactions between capsid pentamers and RNA subdomains. To test our method, we tackle the satellite tobacco mosaic virus (STMV) genome, which has been widely studied by both experimental and computational communities. We provide not only a methodology to structurally analyze the tertiary conformations of the RNA genome inside capsids, but a flexible platform that allows the easy implementation of features/descriptors coming from both theoretical and experimental approaches.


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