| First Author | Rehfeld F | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 1235 |
| PubMed ID | 29581509 | Mgi Jnum | J:281208 |
| Mgi Id | MGI:6378035 | Doi | 10.1038/s41467-018-03681-3 |
| Citation | Rehfeld F, et al. (2018) The RNA-binding protein ARPP21 controls dendritic branching by functionally opposing the miRNA it hosts. Nat Commun 9(1):1235 |
| abstractText | About half of mammalian miRNA genes lie within introns of protein-coding genes, yet little is known about functional interactions between miRNAs and their host genes. The intronic miRNA miR-128 regulates neuronal excitability and dendritic morphology of principal neurons during mouse cerebral cortex development. Its conserved host genes, R3hdm1 and Arpp21, are predicted RNA-binding proteins. Here we use iCLIP to characterize ARPP21 recognition of uridine-rich sequences with high specificity for 3'UTRs. ARPP21 antagonizes miR-128 activity by co-regulating a subset of miR-128 target mRNAs enriched for neurodevelopmental functions. Protein-protein interaction data and functional assays suggest that ARPP21 acts as a positive post-transcriptional regulator by interacting with the translation initiation complex eIF4F. This molecular antagonism is reflected in inverse activities during dendritogenesis: miR-128 overexpression or knockdown of ARPP21 reduces dendritic complexity; ectopic ARPP21 leads to an increase. Thus, we describe a unique example of convergent function by two products of a single gene. |
