SmD1 Modulates the miRNA Pathway Independently of Its Pre-mRNA Splicing Function

摘要: microRNAs (miRNAs) are a class of endogenous regulatory RNAs that play key role in myriad biological processes. Upon transcription, primary miRNA transcripts sequentially processed by Drosha and Dicer ribonucleases into ~22–24 nt miRNAs. Subsequently, miRNAs incorporated the RNA-induced silencing complexes (RISCs) contain Argonaute (AGO) family proteins guide RISC to target via complementary base pairing, leading post-transcriptional gene combination translation inhibition mRNA destabilization. Select pre-mRNA splicing factors have been implicated small RNA-mediated pathways fission yeast, worms, flies mammals, but underlying molecular mechanisms not well understood. Here, we show SmD1, core component Drosophila nuclear ribonucleoprotein particle (snRNP) splicing, is required for biogenesis function. SmD1 interacts with both microprocessor Pasha pri-miRNAs, indispensable optimal biogenesis. Depletion impairs assembly function miRISC without significantly affecting expression major canonical pathway components. Moreover, physically functionally associates components miRISC, including AGO1 GW182. Notably, defects resulting from can be uncoupled machineries distinct entities. Finally, photoactivatable-ribonucleoside-enhanced crosslinking immunoprecipitation (PAR-CLIP) analysis identifies numerous SmD1-binding events across transcriptome reveals direct SmD1-miRNA interactions. Our study suggests plays miRNA-mediated independently its activity indicates dual roles regulation may evolutionarily widespread.