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Nat Commun. 2018 Mar 26;9(1):1235. doi: 10.1038/s41467-018-03681-3.

The RNA-binding protein ARPP21 controls dendritic branching by functionally opposing the miRNA it hosts.

Author information

1
Institute for Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
2
Department of Computer Science, Albert-Ludwigs-Universität Freiburg, Georges-Köhler-Allee 106, 79110, Freiburg im Breisgau, Germany.
3
Institute for Integrative Neuroanatomy, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
4
Institute for Chemistry and Biochemistry, Freie Universität Berlin, Thielallee 63, 14195, Berlin, Germany.
5
Institute for Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany. gregory.wulczyn@charite.de.

Abstract

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.

PMID:
29581509
PMCID:
PMC5964322
DOI:
10.1038/s41467-018-03681-3
[Indexed for MEDLINE]
Free PMC Article

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