Structural basis of transcriptional repression by SRA, a long non-coding RNA

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04339
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Tokyo Metropolitan University
• Principal Investigator: MISHIMA Masaki 首都大学東京, 理工学研究科, 准教授 (70346310)
• Co-Investigator(Kenkyū-buntansha): 田岡 万悟 首都大学東京, 理工学研究科, 准教授 (60271160) ; 藤原 俊伸 近畿大学, 薬学部, 教授 (80362804) ; 河原 行郎 大阪大学, 医学系研究科, 教授 (80542563)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: lncRNA / SHARP / SRA / XIST / NMR / RBM15

Outline of Final Research Achievements

SHARP (SMRT/HDAC1-associated repressor protein), a transcriptional co-repressor, which possesses N-terminal RNA recognition motifs (RRMs) and the highly conserved C-terminal domain SPOC domain. The RRM domains of SHARP is known to bind a lnc (long nonconding) RNA, SRA. Meanwhile, SPOC domain binds to SMRT, a component of HDAC (histone deacetylase complex). Previously, we reported that the tertiary structure of the SPOC/phosphorylated SMRT complex and also found that the interaction is phosphorylation dependent. Recently, it has been reported that SHARP binds to the lncRNA XIST RNA which is an essential factor for dosage compensation. In this project, we determined the structure of the RRM1, and performed NMR analyses and RNA binding experiments for RRM2-3-4 and RRM2-3 of SHARP. We also investigated the consensus sequence of SHARP binding using CLIP. We are trying to determine the SHARP/Xist complex, and also started structural study of RBM15, a homolog of SHARP.

Free Research Field

構造生物化学