title: A dual inhibition: microRNA-552 suppresses both transcription and translation of cytochrome P450 2E1.
abstract: MicroRNAs (miRNAs) can direct post-transcriptional or transcriptional gene silencing. Here, we report that miR-552 is in the nucleus and cytosol and inhibits human cytochrome P450 (CYP) 2E1 expression at both transcriptional and post-transcriptional levels. MiR-552 via its non-seed sequence forms hybrids with a loop hairpin of the cruciform structure in CYP2E1 promoter region to inhibit SMARCE1 and RNA polymerase II binding to the promoter and CYP2E1 transcription. Expressing SMARCE1 reverses the inhibitory effects of miR-552 on CYP2E1 mRNA expression. MiR-552 with mutations in non-seed region losses its transcriptional, but retains its post-transcriptional repression to CYP2E1. In contrast, mutation in miR-552 seed sequence suppresses its inhibitory effects on CYP2E1 expression at protein, but not at mRNA, levels. Our results suggest that miR-552 is a miRNA with a dual inhibitory ability at transcriptional and post-transcriptional levels leading to an effective inhibition.
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Miao
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Hailan
authors.initials: H
authors.lastname: Yao
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Chenggang
authors.initials: C
authors.lastname: Li
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Mengfan
authors.initials: M
authors.lastname: Pu
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yao
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xinming
authors.initials: X
authors.lastname: Qi
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: jren@cdser.simm.ac.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Ren
authors.affiliation: The Brain Science Center, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, China. Electronic address: yzwang57@sina.com.
authors.forename: Yizheng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012319:RNA Polymerase II / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C000588992:MIRN552 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C504738:SMARCE1 protein, human; D019392:Cytochrome P-450 CYP2E1; D012319:RNA Polymerase II
keywords: Cytochrome P450 2E1; Gene regulation; MicroRNA; Transcription; Translation