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PMID:29581509
| Citation |
Rehfeld, F, Maticzka, D, Grosser, S, Knauff, P, Eravci, M, Vida, I, Backofen, R and Wulczyn, FG (2018) The RNA-binding protein ARPP21 controls dendritic branching by functionally opposing the miRNA it hosts. Nat Commun 9:1235 |
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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. |
| Links |
PubMed Online version:10.1038/s41467-018-03681-3 |
| Keywords |
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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0005737: cytoplasm |
ECO:0000314: |
C |
ARPP21 localizes to the cytosol and overlaps staining with stress granule. ARPP21 used FLAG-tagg expression in HeLa cells and treated with arsenite Figure 2A,B |
complete | ||||
Notes
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