SUMOylation at K707 of DGCR8 controls direct function of primary microRNA.

Abstract

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.

• Authors: Changhong Zhu, Cheng Chen, Jian Huang, Hailong Zhang, Xian Zhao, Rong Deng, Jinzhuo Dou, Hui Jin, Ran Chen, Ming Xu, Qin Chen, Yanli Wang, Jianxiu Yu
• Journal: Nucleic acids research (Nucleic Acids Res) Vol. 43 Issue 16 Pg. 7945-60 (Sep 18 2015) ISSN: 1362-4962 [Electronic] England
• PMID: 26202964 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Chemical References

• DGCR8 protein, human
• MicroRNAs
• RNA-Binding Proteins
• SUMO-1 Protein
• Lysine

Topics

• Animals
• Carcinogenesis
• Cell Line
• Cell Movement
• Cells, Cultured
• Humans
• Lysine (metabolism)
• Mice
• Mice, Nude
• MicroRNAs (metabolism)
• Neoplasms (metabolism, physiopathology)
• Phosphorylation
• Protein Stability
• RNA-Binding Proteins (chemistry, metabolism)
• SUMO-1 Protein (metabolism)
• Sumoylation
• Ubiquitination