Journal
NUCLEIC ACIDS RESEARCH
Volume 43, Issue 16, Pages 7945-7960Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkv741
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Funding
- National Key Program for Basic Research of China [2011CB811303, 2012CB917101]
- National Natural Science Foundation [81472571, 91129726, 81171941]
- Innovation Program of Shanghai Municipal Education Commission [12YZ033]
- The Ph.D. Programs Foundation of Ministry of Education of China [20120073110070]
- Doctoral Innovation Fund Projects from Shanghai Jiao Tong University School of Medicine [BXJ201202]
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DGCR8 (DiGeorge syndrome critical region gene 8) is essential for primary microRNA (pri-miRNA) processing in the cell nucleus. It specifically combines with Drosha, a nuclear RNase III enzyme, to form the Microprocessor complex (MC) that cleaves pri-miRNA to precursor miRNA (pre-miRNA), which is further processed to mature miRNA by Dicer, a cytoplasmic RNase III enzyme. Increasing evidences suggest that pri-/pre-miRNAs have direct functions in regulation of gene expression, however the underlying mechanism how it is fine-tuned remains unclear. Here we find that DGCR8 is modified by SUMO1 at the major site K-707, which can be promoted by its ERK-activated phosphorylation. SUMOylation of DGCR8 enhances the protein stability by preventing the degradation via the ubiquitin proteasome pathway. More importantly, SUMOylation of DGCR8 does not alter its association with Drosha, the MC activity and miRNA biogenesis, but rather influences its affinity with pri-miRNAs. This altered affinity of DGCR8 with pri-miRNAs seems to control the direct functions of pri-miRNAs in recognition and repression of the target mRNAs, which is evidently linked to the DGCR8 function in regulation of tumorigenesis and cell migration. Collectively, our data suggest a novel mechanism that SUMOylation of DGCR8 controls direct functions of pri-miRNAs in gene silencing.
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