The Strand-biased Transcription of SARS-CoV-2 and Unbalanced Inhibition by Remdesivir
Abstract SARS-CoV-2, a positive single-stranded RNA virus, caused the COVID-19 pandemic. During the viral replication and transcription, the RNA dependent RNA polymerase (RdRp) “jumps” along the genome template, resulting in discontinuous negative-stranded transcripts. In other coronaviruses, the negative strand RNA was found functionally relevant to the activation of host innate immune responses. Although the sense-mRNA architectures of SARS-CoV-2 were reported, its negative strand was unexplored. Here, we deeply sequenced both strands of RNA and found SARS-CoV-2 transcription is strongly biased to form the sense strand. During negative strand synthesis, apart from canonical sub-genomic ORFs, numerous non-canonical fusion transcripts are formed, driven by 3-15 nt sequence homology scattered along the genome but more prone to be inhibited by SARS-CoV-2 RNA polymerase inhibitor Remdesivir. The drug also represses more of the negative than the positive strand synthesis as supported by a mathematic simulation model and experimental quantifications. Overall, this study opens new sights into SARS-CoV-2 biogenesis and may facilitate the anti-viral vaccine development and drug design.One Sentence Summary Strand-biased transcription of SARS-CoV-2..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
bioRxiv.org - (2021) vom: 15. Dez. Zur Gesamtaufnahme - year:2021 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhao, Yan [VerfasserIn] |
|---|
| Links: |
|---|
| doi: |
10.1101/2020.10.15.325050 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI019131356 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI019131356 | ||
| 003 | DE-627 | ||
| 005 | 20230429091826.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 201016s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2020.10.15.325050 |2 doi | |
| 035 | |a (DE-627)XBI019131356 | ||
| 035 | |a (biorXiv)10.1101/2020.10.15.325050 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | |a 570 |q DE-84 | |
| 100 | 1 | |a Zhao, Yan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a The Strand-biased Transcription of SARS-CoV-2 and Unbalanced Inhibition by Remdesivir |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract SARS-CoV-2, a positive single-stranded RNA virus, caused the COVID-19 pandemic. During the viral replication and transcription, the RNA dependent RNA polymerase (RdRp) “jumps” along the genome template, resulting in discontinuous negative-stranded transcripts. In other coronaviruses, the negative strand RNA was found functionally relevant to the activation of host innate immune responses. Although the sense-mRNA architectures of SARS-CoV-2 were reported, its negative strand was unexplored. Here, we deeply sequenced both strands of RNA and found SARS-CoV-2 transcription is strongly biased to form the sense strand. During negative strand synthesis, apart from canonical sub-genomic ORFs, numerous non-canonical fusion transcripts are formed, driven by 3-15 nt sequence homology scattered along the genome but more prone to be inhibited by SARS-CoV-2 RNA polymerase inhibitor Remdesivir. The drug also represses more of the negative than the positive strand synthesis as supported by a mathematic simulation model and experimental quantifications. Overall, this study opens new sights into SARS-CoV-2 biogenesis and may facilitate the anti-viral vaccine development and drug design.One Sentence Summary Strand-biased transcription of SARS-CoV-2. | ||
| 700 | 1 | |a Sun, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yunfei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhengxuan |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Ruoqing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jincun |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Yuhui |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2021) vom: 15. Dez. |
| 773 | 1 | 8 | |g year:2021 |g day:15 |g month:12 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.isci.2021.102857 |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.10.15.325050 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2021 |b 15 |c 12 | ||
| 953 | |2 045F |a 570 | ||