Secondary structure of the SARS-CoV-2 5’-UTR

Miao, Zhichao; Tidu, Antonin; Eriani, Gilbert; Martin, Franck

doi:10.1080/15476286.2020.1814556

Cited by 134 publications

(187 citation statements)

References 44 publications

(62 reference statements)

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“…To date, efforts have been made to elucidate the SARS-CoV-2 RNA element structures in silico [ 9 , 10 ] and by chemical or enzymatic probing for the full or partial RNA genome in virus-infected cells [ 11 , 12 , 13 , 14 ] and in vitro [ 12 , 15 , 16 , 17 ]. We herein report the RNA structure of SARS-CoV-2 3′ UTR by using a chemical probing strategy, namely dimethyl sulfate (DMS)-mutational profiling with sequencing (MaPseq) [ 18 ] in virions and minigene-transfected cells.…”

Section: Introductionmentioning

confidence: 99%

The RNA Architecture of the SARS-CoV-2 3′-Untranslated Region

Zhao

Qiu

Aryal

et al. 2020

Viruses

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. The 3′ untranslated region (UTR) of this β-CoV contains essential cis-acting RNA elements for the viral genome transcription and replication. These elements include an equilibrium between an extended bulged stem-loop (BSL) and a pseudoknot. The existence of such an equilibrium is supported by reverse genetic studies and phylogenetic covariation analysis and is further proposed as a molecular switch essential for the control of the viral RNA polymerase binding. Here, we report the SARS-CoV-2 3′ UTR structures in cells that transcribe the viral UTRs harbored in a minigene plasmid and isolated infectious virions using a chemical probing technique, namely dimethyl sulfate (DMS)-mutational profiling with sequencing (MaPseq). Interestingly, the putative pseudoknotted conformation was not observed, indicating that its abundance in our systems is low in the absence of the viral nonstructural proteins (nsps). Similarly, our results also suggest that another functional cis-acting element, the three-helix junction, cannot stably form. The overall architectures of the viral 3′ UTRs in the infectious virions and the minigene-transfected cells are almost identical.

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Section: Introductionmentioning

confidence: 99%

The RNA Architecture of the SARS-CoV-2 3′-Untranslated Region

Zhao

Qiu

Aryal

et al. 2020

Viruses

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“…These UTRs are relatively short, being approximately 230 bases, but have important regulatory functions [21]. The 5′ UTR is highly structured and thought to contain 5 stem-loop (SL1-SL5) structures, with the SL3 structure also housing the transcriptional regulation sequence (TRS-L) important for generation of subgenomic mRNAs [22]. Each gene in the genome also has its own upstream TRS-B sequence.…”

Section: Sars-cov-2 Derives From Bat Covs and Is Closely Related To Smentioning

confidence: 99%

Decoding Covid-19 with the SARS-CoV-2 Genome

et al. 2021

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“…SL-III contains the translation-regulatory sequence (TRS), which is essential for the discontinuous transcription of ORF1ab. SL-5 is crucial for the viral RNA packaging and translation of the ORF1ab polyprotein (10,11,12). The 3'-UTR of coronaviruses is important for viral replication (RNA synthesis and translation).…”

Section: Sars-cov-2 Contains a 260-nucleotide Long 5'-utr And A 200 Nmentioning

confidence: 99%

RNA-protein interaction analysis of SARS-CoV-2 5’- and 3’-untranslated regions identifies an antiviral role of lysosome-associated membrane protein-2

Verma

Saha

Kumar

et al. 2021

Preprint

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Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a positive-strand RNA virus. Viral genome is capped at the 5’-end, followed by an untranslated region (UTR). There is poly-A tail at 3’-end, preceded by an UTR. Self-interaction between the RNA regulatory elements present within 5’- and 3’-UTRs as well as their interaction with host/virus-encoded proteins mediate the function of 5’- and 3’-UTRs. Using RNA-protein interaction detection (RaPID) assay coupled to liquid chromatography with tandem mass-spectrometry, we identified host interaction partners of SARS-CoV-2 5’- and 3’-UTRs and generated an RNA-protein interaction network. By combining these data with the previously known protein-protein interaction data proposed to be involved in virus replication, we generated the RNA-protein-protein interaction (RPPI) network, likely to be essential for controlling SARS-CoV-2 replication. Notably, bioinformatics analysis of the RPPI network revealed the enrichment of factors involved in translation initiation and RNA metabolism. Lysosome-associated membrane protein-2a (Lamp2a) was one of the host proteins that interact with the 5’-UTR. Further studies showed that Lamp2 level is upregulated in SARS-CoV-2 infected cells and overexpression of Lamp2a and Lamp2b variants reduced viral RNA level in infected cells and vice versa. In summary, our study provides an useful resource of SARS-CoV-2 5’- and 3’-UTR binding proteins and reveal the antiviral function of host Lamp2 protein.ImportanceReplication of a positive-strand RNA virus involves an RNA-protein complex consisting of viral genomic RNA, host RNA(s), virus-encoded proteins and host proteins. Dissecting out individual components of the replication complex will help decode the mechanism of viral replication. 5’- and 3’-UTRs in positive-strand RNA viruses play essential regulatory roles in virus replication. Here, we identified the host proteins that associate with the UTRs of SARS-CoV-2, combined those data with the previously known protein-protein interaction data (expected to be involved in virus replication) and generated the RNA-protein-protein interaction (RPPI) network. Analysis of the RPPI network revealed the enrichment of factors involved in translation initiation and RNA metabolism, which are important for virus replication. Analysis of one of the interaction partners of the 5’-UTR (Lamp2a) demonstrated its antiviral role in SARS-CoV-2 infected cells. Collectively, our study provides a resource of SARS-CoV-2 UTR-binding proteins and identifies an antiviral role of host Lamp2a protein.

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Secondary structure of the SARS-CoV-2 5’-UTR

Cited by 134 publications

References 44 publications

The RNA Architecture of the SARS-CoV-2 3′-Untranslated Region

The RNA Architecture of the SARS-CoV-2 3′-Untranslated Region

Decoding Covid-19 with the SARS-CoV-2 Genome

RNA-protein interaction analysis of SARS-CoV-2 5’- and 3’-untranslated regions identifies an antiviral role of lysosome-associated membrane protein-2

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