Analysis of selenoprotein P translational regulation by endogenous antisense RNA

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18707
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Food science
• Research Institution: University of Miyazaki (2017-2018); Doshisha University (2016)
• Principal Investigator: Mita Yuichiro 宮崎大学, 医学部, 研究員 (70609122)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: noncoding RNA / セレノプロテインＰ / 翻訳 / SECIS

Outline of Final Research Achievements

The Sec insertion sequence (SECIS) is present in the mRNA of the Sec-containing protein. The binding of SBP2 to SECIS induce Sec insert into the protein. A related long ncRNA (L-IST) exists in selenoprotein P (SeP) which is one of the Sec-containing proteins. Therefore, we examined the influence of L-IST on SeP. When L-IST was expressed in HepG2 cells, the expression level of protein decreased in a SeP mRNA-independent manner. The mechanism was translational repression by the binding inhibition of SeP mRNA and SBP2. From the above results, L-IST is a novel ncRNA and L-IST can inhibit the function of SECIS and suppresses the translation of SeP mRNA.

Free Research Field

noncoding RNA

Academic Significance and Societal Importance of the Research Achievements

糖尿病で増加し、糖尿病を増悪させる因子として知られているSelenoprotein P(SeP)のタンパク質レベルを抑制する新規のnoncoding RNAであるL-ISTを発見し、メカニズムの解析を行った。その結果、L-ISTはSeP mRNAの翻訳段階を特異的に抑制することが分かった。SePはSECISを利用するという特殊な翻訳様式を示しており、L-ISTを標的にすることにより血中SeP高値の糖尿病患者への副作用の少ない糖尿病治療法を開発できる可能性がある。