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2021 Fiscal Year Final Research Report

Epigenetic regulation based on non-coding RNA in HBV infection

Research Project

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Project/Area Number 20K17064
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionNational Institute of Infectious Diseases (2021)
Tokai University (2020)

Principal Investigator

Kakizaki Masatoshi  国立感染症研究所, ウイルス第三部, 研究員 (00778954)

Project Period (FY) 2020-04-01 – 2022-03-31
KeywordsHBV / エピジェネティック制御 / ノンコーディングRNA / 反復配列
Outline of Final Research Achievements

This study aims to elucidate the mechanism by which repetitive sequences in host-derived non-coding RNAs (ncRNAs) that interact with cccDNA repress pgRNA transcription through epigenetic regulation. In this study, we found that the regulation of pgRNA transcription by repetitive sequences is caused by methylation of histones H3K9 and H3K27. Using orbitrap LC-MS analysis, we also comprehensively identified proteins that interact with repetitive sequences. Furthermore, using siRNAs against mRNAs of the identified proteins, we screened for proteins involved in pgRNA transcriptional repression and found two candidates.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

本研究では、宿主由来のncRNAに含まれる反復配列がウイルス再活性化の原因となっているcccDNAからのpgRNA転写を制御するメカニズムを解明を目指している。今回、我々の研究で、この反復配列があるタンパク質と相互作用することでH3K9とH3K27のメチル化を促進していることが明らかになった。このことは、今後のHBVの新たな治療開発に繋がるとともに、pgRNAの新たな転写制御メカニズムの発見ともなり学術的意義も大きと考えられる。

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Published: 2023-01-30  

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