The RNA-binding protein ARPP21 controls dendritic branching by functionally opposing the miRNA it hosts
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
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Nature communications. - 9, 1 (2018) , 1235, ISSN: 2041-1723
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2020
- Urheber
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Rehfeld, Frederick
Maticzka, Daniel
Grosser, Sabine
Knauff, Pina Luzia
Eravci, Murat
Vida, Imre
Backofen, Rolf
Wulczyn, Gregory
- Beteiligte Personen und Organisationen
- DOI
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10.1038/s41467-018-03681-3
- URN
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urn:nbn:de:bsz:25-freidok-1708115
- Rechteinformation
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Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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14.08.2025, 10:44 MESZ
Datenpartner
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Beteiligte
- 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
Entstanden
- 2020