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

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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

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Notes: Nature communications. - 9, 1 (2018) , 1235, ISSN: 2041-1723

Event: Veröffentlichung

(where): Freiburg

(who): Universität

(when): 2020

Creator: Rehfeld, Frederick
Maticzka, Daniel
Grosser, Sabine
Knauff, Pina Luzia
Eravci, Murat
Vida, Imre
Backofen, Rolf
Wulczyn, Gregory

Contributor: Albert-Ludwigs-Universität Freiburg. Professur für Bioinformatik

DOI: 10.1038/s41467-018-03681-3

URN: urn:nbn:de:bsz:25-freidok-1708115

Rights: Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 25.03.2025, 1:43 PM CET

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Associated

Rehfeld, Frederick
Maticzka, Daniel
Grosser, Sabine
Knauff, Pina Luzia
Eravci, Murat
Vida, Imre
Backofen, Rolf
Wulczyn, Gregory
Albert-Ludwigs-Universität Freiburg. Professur für Bioinformatik
Universität

Time of origin

2020

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

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