The RNA-binding protein ARPP21 controls dendritic branching by functionally opposing the miRNA it hosts.
Frederick RehfeldDaniel MaticzkaSabine GrosserPina KnauffMurat EravciImre VidaRolf BackofenF Gregory WulczynPublished in: Nature communications (2018)
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.
Keyphrases
- cell proliferation
- long non coding rna
- genome wide
- genome wide identification
- protein protein
- long noncoding rna
- transcription factor
- binding protein
- genome wide analysis
- bioinformatics analysis
- small molecule
- dna methylation
- gene expression
- copy number
- functional connectivity
- single molecule
- big data
- deep learning
- blood brain barrier
- genetic diversity