AGO CLIP-based imputation of potent siRNA sequences targeting SARS-CoV-2 with antifibrotic miRNA-like activity
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Ahn, Seung Hyun | - |
dc.contributor.author | Gu, Dowoon | - |
dc.contributor.author | Koh, Yongjun | - |
dc.contributor.author | Lee, Hye-Sook | - |
dc.contributor.author | Chi, Sung Wook | - |
dc.date.accessioned | 2022-02-19T03:40:30Z | - |
dc.date.available | 2022-02-19T03:40:30Z | - |
dc.date.created | 2022-02-08 | - |
dc.date.issued | 2021-09-27 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/136303 | - |
dc.description.abstract | Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with fatal pulmonary fibrosis. Small interfering RNAs (siRNAs) can be developed to induce RNA interference against SARS-CoV-2, and their susceptible target sites can be inferred by Argonaute crosslinking immunoprecipitation sequencing (AGO CLIP). Here, by reanalysing AGO CLIP data in RNA viruses, we delineated putative AGO binding in the conserved non-structural protein 12 (nsp12) region encoding RNA-dependent RNA polymerase (RdRP) in SARS-CoV-2. We utilised the inferred AGO binding to optimise the local RNA folding parameter to calculate target accessibility and predict all potent siRNA target sites in the SARS-CoV-2 genome, avoiding sequence variants. siRNAs loaded onto AGO also repressed seed (positions 2-8)-matched transcripts by acting as microRNAs (miRNAs). To utilise this, we further screened 13 potential siRNAs whose seed sequences were matched to known antifibrotic miRNAs and confirmed their miRNA-like activity. A miR-27-mimicking siRNA designed to target the nsp12 region (27/RdRP) was validated to silence a synthesised nsp12 RNA mimic in lung cell lines and function as an antifibrotic miR-27 in regulating target transcriptomes related to TGF-beta signalling. siRNA sequences with an antifibrotic miRNA-like activity that could synergistically treat COVID-19 are available online (http://clip.korea.ac.kr/covid19). | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PORTFOLIO | - |
dc.subject | RNA INTERFERENCE | - |
dc.subject | REGULATOR | - |
dc.title | AGO CLIP-based imputation of potent siRNA sequences targeting SARS-CoV-2 with antifibrotic miRNA-like activity | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Chi, Sung Wook | - |
dc.identifier.doi | 10.1038/s41598-021-98708-z | - |
dc.identifier.scopusid | 2-s2.0-85115782318 | - |
dc.identifier.wosid | 000700619200002 | - |
dc.identifier.bibliographicCitation | SCIENTIFIC REPORTS, v.11, no.1 | - |
dc.relation.isPartOf | SCIENTIFIC REPORTS | - |
dc.citation.title | SCIENTIFIC REPORTS | - |
dc.citation.volume | 11 | - |
dc.citation.number | 1 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | REGULATOR | - |
dc.subject.keywordPlus | RNA INTERFERENCE | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.