Altered RNA in neurons and its link to brain environment

2015 Fiscal Year Final Research Report

• Project Area: Brain Environment
• Project/Area Number: 23111005
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Institute of Physical and Chemical Research (2013-2015); Hiroshima University (2011-2012)
• Principal Investigator: Takumi Toru 国立研究開発法人理化学研究所, 脳科学総合研究センター, シニアチームリーダー (00222092)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: RNA結合タンパク質 / RNAスプライシング / 細胞骨格 / アクチン / 筋萎縮性側索硬化症 / 精神神経疾患

Outline of Final Research Achievements

Translocated in liposarcoma/Fused in sarcoma (TLS/FUS) is an RNA-binding protein that regulates the splicing pattern of mRNA transcripts and is known to cause a type of familial amyotrophic lateral sclerosis (ALS). In the absence of TLS, Mammalian enabled (Mena), an actin-regulatory protein and a target of TLS, undergoes preferential alternative splicing. We showed that the ablation of TLS dysregulates the subcellular location and functions of Mena. When TLS knockout mouse embryonic fibroblasts (MEFs) were transfected with wild type Mena, it no longer accumulated at focal adhesions and peripheral structures, whereas the localization of the alternatively spliced form was maintained. Additionally, Mena’s ability to suppress the motility of cells was lost in TLS knockout MEFs. Moreover, Mena failed to promote neurite outgrowth in TLS knockout primary neurons. Taken together, TLS is intimately involved in the local cytoskeletal dynamics surrounding Mena in both fibroblasts and neurons.

Free Research Field

脳科学