Weiss, Kerstin and Treiber, Thomas and Meister, Gunter and Schratt, Gerhard (2019) The nuclear matrix protein Matr3 regulates processing of the synaptic microRNA-138-5p. NEUROBIOLOGY OF LEARNING AND MEMORY, 159. pp. 36-45. ISSN 1074-7427, 1095-9564
Full text not available from this repository. (Request a copy)Abstract
microRNA-dependent post-transcriptional control represents an important gene-regulatory layer in post-mitotic neuronal development and synaptic plasticity. We recently identified the brain-enriched miR-138 as a negative regulator of dendritic spine morphogenesis in rat hippocampal neurons. A potential involvement of miR-138 in cognition is further supported by a recent GWAS study on memory performance in a cohort of aged (>60 years) individuals. The expression of miR-138, which is encoded in two independent genomic loci (miR-138-1 and -2), is subject to both cell-type and developmental stage-specific regulation, the underlying molecular mechanisms however are poorly understood. Here, we show that miR-138-2 is the primary source of mature miR-138 in developing rat hippocampal neurons. Furthermore, we obtained evidence for the regulation of miR-138-2 biogenesis at the level of primary miRNA processing. Using biochemical pull-down assays, we identified the nuclear matrix protein Matrin-3 as pri/pre-miR-138 interacting protein and mapped the interaction to the pri/pre-miR-138-2 loop region. Matrin-3 loss-of-function experiments in HEK293 cells and primary neurons together with protein localization studies suggest an inhibitory function of Matrin-3 in nuclear pri-miR-138-2 processing. Together, our experiments unravel a new mechanism of miR-138 regulation in neurons, with important implications for miR-138 regulation during neuronal development, synaptic plasticity and memory-related processes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DEGRADATION; RNAS; microRNA; miR-138; Matrin-3; RNA-binding protein; Synaptic plasticity |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Apr 2020 06:51 |
| Last Modified: | 16 Apr 2020 06:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27431 |
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