A dual inhibition: microRNA-552 suppresses both transcription and translation of cytochrome P450 2E1

Biochim Biophys Acta. 2016 Apr;1859(4):650-62. doi: 10.1016/j.bbagrm.2016.02.016. Epub 2016 Feb 27.

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.

Keywords: Cytochrome P450 2E1; Gene regulation; MicroRNA; Transcription; Translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomal Proteins, Non-Histone / genetics
  • Cytochrome P-450 CYP2E1 / biosynthesis*
  • Cytochrome P-450 CYP2E1 / genetics
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation
  • Gene Silencing
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mutation
  • Promoter Regions, Genetic
  • Protein Biosynthesis*
  • RNA Polymerase II / genetics
  • RNA, Messenger / biosynthesis
  • Transcription, Genetic*

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MIRN552 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • SMARCE1 protein, human
  • Cytochrome P-450 CYP2E1
  • RNA Polymerase II