Evidence for a cytoplasmic microprocessor of pri-miRNAs

Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
RNA (Impact Factor: 4.94). 05/2012; 18(7):1338-46. DOI: 10.1261/rna.032268.112
Source: PubMed


microRNAs (miRNAs) represent a class of noncoding RNAs that fine-tune gene expression through post-transcriptional silencing. While miRNA biogenesis occurs in a stepwise fashion, initiated by the nuclear microprocessor, rare noncanonical miRNAs have also been identified. Here we characterize the molecular components and unique attributes associated with the processing of virus-derived cytoplasmic primary miRNAs (c-pri-miRNAs). RNA in situ hybridization and inhibition of cellular division demonstrated a complete lack of nuclear involvement in c-pri-miRNA cleavage while genetic studies revealed that maturation still relied on the canonical nuclear RNase III enzyme, Drosha. The involvement of Drosha was mediated by a dramatic relocalization to the cytoplasm following virus infection. Deep sequencing analyses revealed that the cytoplasmic localization of Drosha does not impact the endogenous miRNA landscape during infection, despite allowing for robust synthesis of virus-derived miRNAs in the cytoplasm. Taken together, this research describes a unique function for Drosha in the processing of highly structured cytoplasmic RNAs in the context of virus infection.

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Available from: Benjamin R Tenoever, Nov 03, 2014
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    • "Alternatively, miRNA biosynthesis may be globally downregulated. Shapiro et al. demonstrated that upon infection with an RNA virus, Drosha is dramatically relocalized to the cytoplasm [84]. Others also reported global dampening of miRNA expression in productive viral infections, perhaps in an effort to enhance the immediate interferon response [41], [42]. "
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    • "This would be a novel mechanism, by which cytoplasmic pri-miRNA transcripts function in a negative feedback-back loop to regulate miRNA function. Another possibility is that pri-miRNAs are processed in the cytoplasm, similar to Drosha-mediated processing of viral pri-miRNAs that was shown to take place in the cytoplasm [45]. In these cells relocalization of Drosha to the cytoplasm and the subsequent pri-miRNA processing was triggered by viral infection. "
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