Increased precursor microRNA-21 following status epilepticus can compete with mature microRNA-21 to alter translation.
Kayam Chak, Biswajoy Roy-Chaudhuri, Hak Kyun Kim, Kayla C Kemp, Brenda E Porter, Mark A Kay
Author Information
Kayam Chak: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA USA.
Biswajoy Roy-Chaudhuri: Departments of Pediatrics and Genetics, Stanford University, Stanford, CA USA.
Hak Kyun Kim: Departments of Pediatrics and Genetics, Stanford University, Stanford, CA USA.
Kayla C Kemp: Departments of Pediatrics and Genetics, Stanford University, Stanford, CA USA.
Brenda E Porter: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA USA. Electronic address: brenda2@stanford.edu.
Mark A Kay: Departments of Pediatrics and Genetics, Stanford University, Stanford, CA USA.
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.
