title: MicroRNA 125 represses nonsense-mediated mRNA decay by regulating SMG1 expression.
abstract: Nonsense-mediated mRNA decay (NMD) is a cellular response mechanism that eliminates aberrant mRNA transcripts and thereby prevents the production of potentially deleterious C-terminally truncated proteins. The phosphatidylinositol 3-kinase-related protein kinase SMG1 is considered to be an essential factor in the NMD pathway. We demonstrate that the brain-enriched microRNA, miRNA-125 (miRNA-125a and miRNA-125b) is a bona fide negative regulator of SMG1 in humans. Down-regulation of SMG1 expression is mediated by miRNA-125 binding to a microRNA response element in the 3' untranslated region of SMG1 mRNA, which leads to degradation of the SMG1 mRNA. In human cells, overexpression of miR-125 represses the endogenous levels of SMG1 protein and suppresses the NMD pathway; however, knockdown of miR-125 up-regulates the NMD pathway. These results suggest the existence of an RNA circuit linking the microRNA and NMD pathways.
authors.affiliation: Key Laboratory of Chemical Biology and Molecular Engineering, Ministry of Education, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Bowen
authors.initials: B
authors.lastname: Jiang
authors.forename: Chenliang
authors.initials: C
authors.lastname: Jia
authors.forename: Baofeng
authors.initials: B
authors.lastname: Chai
authors.forename: Aihua
authors.initials: A
authors.lastname: Liang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D015536:Down-Regulation; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D059365:Nonsense Mediated mRNA Decay / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; C531888:MIRN125 microRNA, human; C514704:SMG1 protein, human