Identification of the key nucleases in miRNA mediated mRNA deadenylation

On Jan 11, 2010, the Molecular and Cellular Biology published online the latest research on mechanisms of miRNA-mediated mRNA degradation. This work was carried out by graduate student Xianghua Piao and Xue Zhang as collaboration between the laboratories of Dr. Ligang Wu at Institute of Biochemistry and Cell Biology, SIBS, CAS and Dr. Joel Belasco at New York University.

 

MicroRNAs (miRNAs) are small (~22-nucleotide) non-coding RNAs, which play a crucial role in eukaryotic gene regulation. miRNAs repress gene expression post-transcriptionally by inhibiting translation and by expediting deadenylation so as to trigger rapid mRNA decay. However, it is not known how miRNA accelerates poly(A) removal, which is the first and rate-limiting step of miRNA-mediated mRNA degradation. In this study, researchers identified CAF1 and POP2, the members of CCR4-NOT complex, as the major nucleases responsible for miRNA-mediated mRNA deadenylation. Interestingly, they show that CAF1 also play an important role in "off-target" effect of RNA interference (RNAi). Moreover, this study also implied that RNA-induced silencing complex (RISC) likely facilitates deadenylation by changing the conformation of mRNP, making the autonomous encounters of CCR4-NOT with poly(A) more productive, rather by directly recruiting CCR4-NOT. These findings laid the foundation for understanding the fate-decision of mRNAs by miRNA in mammalian cells.

 

This study was supported by grants from National Natural Science Foundation of China and the Chinese Academy of Sciences.