Increased precursor microRNA-21 following status epilepticus can compete with mature microRNA-21 to alter translation
| Autor: | Kayla C Kemp, Hak Kyun Kim, Kayam Chak, Mark A. Kay, Brenda E. Porter, Biswajoy Roy-Chaudhuri |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Time Factors Receptor expression Status epilepticus Biology Muscarinic Agonists Protein Serine-Threonine Kinases Epileptogenesis Article 03 medical and health sciences Mice 0302 clinical medicine Status Epilepticus Developmental Neuroscience Neurotrophin 3 microRNA medicine Animals Humans Nerve Growth Factors RNA Messenger Binding site Psychological repression Messenger RNA Binding Sites Pilocarpine Receptor Transforming Growth Factor-beta Type II Computational Biology Translation (biology) Cell biology Rats Up-Regulation Disease Models Animal MicroRNAs 030104 developmental biology Neurology Biochemistry Protein Biosynthesis medicine.symptom Receptors Transforming Growth Factor beta 030217 neurology & neurosurgery |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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