Fig. 8
Schematic depiction of our model for the miR-128-ARPP21 regulatory circuit and its impact on the post-transcriptional regulation of common mRNA targets. a ARPP21 and miR-128 are co-expressed from the same genetic locus. pri-miR-128-2 is generated upon Arpp21 transcription and subsequently processed by Drosha and Dicer into mature miR-128. miR-128-loaded miRISC binds and downregulates target mRNAs that possess the miR-128 seed match sequence. Arpp21 is transcribed, spliced, and translated into protein. ARPP21 binds a subset of miR-128 target mRNAs via a uridine-rich sequence motif leading to increased protein expression. Mechanisms that could potentially regulate the relative activities of ARPP21 and miR-128 are marked in red. Alternative splicing of the Arpp21 mRNA and phosphorylation of ARPP21 protein could regulate its activity. Further, miR-128 can inhibit Arpp21 expression through a conserved seed match in the Arpp21 3′UTR. On the other hand, miR-128 processing is regulated during development. b Co-regulated transcripts have a greater dynamic range of gene expression compared to transcripts under control of either miR-128 or ARPP21 acting on their own. Dendritic complexity of cortical neurons is highly sensitive to the relative levels of miR-128 and ARPP21
