Prof. Hermona Soreq

Neuronal-expressed microRNA-targeted pseudogenes compete with coding genes in the human brain

Barbash, S, Simchovitz A, Buchman AS, Bennett DA, Shifman S, Soreq H.  2017.  

Abstract:

MicroRNAs orchestrate brain functioning via interaction with microRNA recognition elements (MRE) on target transcripts. However, the global impact of potential competition on the microRNA pool between coding and non-coding brain transcripts that share MREs with them remains unexplored. Here we report that non-coding pseudogene transcripts carrying MREs (PSG+MRE) often show duplicated origin, evolutionary conservation and higher expression in human temporal lobe neurons than comparable duplicated MRE-deficient pseudogenes (PSG-MRE). PSG+MRE participate in neuronal RNA-induced silencing complexes (RISC), indicating functional involvement. Furthermore, downregulation cell culture experiments validated bidirectional co-regulation of PSG+MRE with MRE-sharing coding transcripts, frequently not their mother genes, and with targeted microRNAs; also, PSG+MRE single-nucleotide polymorphisms associated with schizophrenia, bipolar disorder and autism, suggesting interaction with mental diseases. Our findings indicate functional roles of duplicated PSG+MRE in brain development and cognition, supporting physiological impact of the reciprocal co-regulation of PSG+MRE with MRE-sharing coding transcripts in human brain neurons.

Journal:

Transl Psychiatry

Volume:

7

Pagination:

e1199

Date Published:

Aug 08

Notes:

2158-3188Barbash, SSimchovitz, ABuchman, A SBennett, D AShifman, SSoreq, HJournal ArticleUnited StatesTransl Psychiatry. 2017 Aug 8;7(8):e1199. doi: 10.1038/tp.2017.163.