The nuclear matrix protein Matr3 regulates processing of the synaptic microRNA-138-5p.
Neurobiol Learn Mem
; 159: 36-45, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30790622
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 (>60â¯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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a RNA
/
Proteínas Associadas à Matriz Nuclear
/
MicroRNAs
/
Hipocampo
/
Plasticidade Neuronal
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article