Modulation of microRNA processing by mismatch repair protein MutLa  

作　　者：Guogen Mao Sanghee Lee Janice Ortega Liya Gu Guo-Min Li 

机构地区：[1]Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, KY 40536, USA [2]Graduate Center for Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, USA [3]Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40536, USA

出　　处：《Cell Research》2012年第6期973-985,共13页细胞研究（英文版）

摘　　要：MicroRNAs （miRNAs） are critical post-transcriptional regulators and are derived from hairpin-snaped primary transcripts via a series of processing steps. However, how the production of individual miRNAs is regulated remains largely unknown. Similarly, loss or overexpression of the key mismatch repair protein MutLa （MLH1-PMS2 heterodimer） leads to genome instability and tumorigenesis, but the mechanisms controlling MutLa expression are unknown. Here we demonstrate in vitro and in vivo that MLH1 and miR-422a participate in a feedback loop that regulates the level of both molecules. Using a defined in-vitro miRNA processing system, we show that MutLa stimulates the conversion of pri-miRo422a to pre-miR-422a, as well as the processing of other miRNAs tested,

关 键 词：mismatch repair MLH1 MutLa MIRNA DROSHA DGCR8 3＇-UTR 

分 类 号：Q522[生物学—生物化学] S816.5[农业科学—饲料科学]