The DPYSL2 gene connects mTOR and schizophrenia.

ABSTRACT: We previously reported a schizophrenia-associated polymorphic CT di-nucleotide repeat (DNR) at the 5'-untranslated repeat (UTR) of DPYSL2, which responds to mammalian target of Rapamycin (mTOR) signaling with allelic differences in reporter assays. Now using microarray analysis, we show that the DNR alleles interact differentially with specific proteins, including the mTOR-related protein HuD/ELAVL4. We confirm the differential binding to HuD and other known mTOR effectors by electrophoretic mobility shift assays. We edit HEK293 cells by CRISPR/Cas9 to carry the schizophrenia risk variant (13DNR) and observe a significant reduction of the corresponding CRMP2 isoform. These edited cells confirm the response to mTOR inhibitors and show a twofold shortening of the cellular projections. Transc

SUBMITTER: Pham X 

PROVIDER: S-EPMC5314117 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature