The role of Mediator and Little Elongation Complex in transcription termination

Nat Commun. 2020 Feb 26;11(1):1063. doi: 10.1038/s41467-020-14849-1.

Abstract

Mediator is a coregulatory complex that regulates transcription of Pol II-dependent genes. Previously, we showed that human Mediator subunit MED26 plays a role in the recruitment of Super Elongation Complex (SEC) or Little Elongation Complex (LEC) to regulate the expression of certain genes. MED26 plays a role in recruiting SEC to protein-coding genes including c-myc and LEC to small nuclear RNA (snRNA) genes. However, how MED26 engages SEC or LEC to regulate distinct genes is unclear. Here, we provide evidence that MED26 recruits LEC to modulate transcription termination of non-polyadenylated transcripts including snRNAs and mRNAs encoding replication-dependent histone (RDH) at Cajal bodies. Our findings indicate that LEC recruited by MED26 promotes efficient transcription termination by Pol II through interaction with CBC-ARS2 and NELF/DSIF, and promotes 3' end processing by enhancing recruitment of Integrator or Heat Labile Factor to snRNA or RDH genes, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Gene Expression Regulation / genetics*
  • HCT116 Cells
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mediator Complex / genetics*
  • Nuclear Proteins / metabolism
  • RNA Cap-Binding Proteins / metabolism
  • RNA Polymerase II / metabolism
  • RNA, Small Nuclear / genetics*
  • Transcription Factors / metabolism
  • Transcription Termination, Genetic / physiology*
  • Transcriptional Elongation Factors / genetics*
  • Transcriptional Elongation Factors / metabolism

Substances

  • MED26 protein, human
  • Mediator Complex
  • NSMF protein, human
  • Nuclear Proteins
  • RNA Cap-Binding Proteins
  • RNA, Small Nuclear
  • SRRT protein, human
  • SUPT5H protein, human
  • Transcription Factors
  • Transcriptional Elongation Factors
  • RNA Polymerase II