Increased precursor microRNA-21 following status epilepticus can compete with mature microRNA-21 to alter translation.

Abstract:

:MicroRNA-21 (miR-21) is consistently up-regulated in various neurological disorders, including epilepsy. Here, we show that the biogenesis of miR-21 is altered following pilocarpine-induced status epilepticus (SE) with an increase in precursor miR-21 (pre-miR-21) in rats. We demonstrate that pre-miR-21 has an energetically favorable site overlapping with the miR-21 binding site and competes with mature miR-21 for binding in the 3'UTR of TGFBR2 mRNA, but not NT-3 mRNA in vitro. This binding competition influences miR-21-mediated repression in vitro and correlates with the increase in TGFBR2 and decrease in NT-3 following SE. Polysome profiling reveals co-localization of pre-miR-21 in the ribosome fraction with translating mRNAs in U-87 cells. The current work suggests that pre-miR-21 may post-transcriptionally counteract miR-21-mediated suppression following SE and could potentially lead to prolonged TGF-β receptor expression impacting epileptogenesis. The study further supports that the ratio of the pre to mature miRNA may be important in determining the regulatory effects of a miRNA gene.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Chak K,Roy-Chaudhuri B,Kim HK,Kemp KC,Porter BE,Kay MA

doi

10.1016/j.expneurol.2016.10.003

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

137-146

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(16)30306-5

journal_volume

286

pub_type

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