The RNA-based mechanism and function underlying molecular diversity in the nervous system

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04277
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokai University
• Principal Investigator: IIJIMA Takatoshi 東海大学, 創造科学技術研究機構, 准教授 (90383702)
• Research Collaborator: SCHEIFFELE Peter Universität Basel, Dept. of Zellbiologie, Biozentrum, Professor ; ULLICH Muller The Scripps Research Institute, Dorris Neuroscience Center, Professor ; CHUNHA Shane UT Health, Department of Integrative Biology and Pharmacology, Professor ; OHTSUKA Masato 東海大学, 医学部, 准教授 (90372945) ; YOSHIDA Tomoyuki 富山大学, 大学院医薬研究科, 准教授 (90372367) ; TANAKA Masami 京都大学, T-CiRA, 博士研究員 (50706182) ; TAKEKOSHI Susumu 東海大学, 医学部, 教授 (70216878)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 選択的スプライシング / RNA結合タンパク質 / 神経細胞 / 3'UTR

Outline of Final Research Achievements

Neuronal alternative splicing is dynamically regulated in a spatiotemporal fashion. We previously found that STAR family proteins (SAM68, SLM1, SLM2) regulate spatiotemporal alternative splicing in the nervous system. However, the whole aspect of alternative splicing programs by STARs remains unclear. Here, we deciphered the alternative splicing programs of SAM68 and SLM1 proteins using transcriptomics. We found that SAM68 controls alternative 3’UTR exons. SAM68 is necessary for proper 3’UTR isoform selection of a novel target, interleukin 1-receptor accessory protein (Il1rap), through alternative last exon (ALE) usage. The ALE usage results in two variants encoding different isoforms, a membrane-bound (mIL1RAcP) and a soluble (sIL1RAcP) type. SAM68 knockout causes conversion from mIL1RAcP into sIL1RAcP in the brain, which significantly disturbs IL1RAcP function. Thus, we uncovered the critical role in proper selection of alternative 3’UTR isoforms by the SAM68 splicing program.

Free Research Field

神経化学