RNA Polymerase II cluster dynamics predict mRNA output in living cells

Elife. 2016 May 3;5:e13617. doi: 10.7554/eLife.13617.

Abstract

Protein clustering is a hallmark of genome regulation in mammalian cells. However, the dynamic molecular processes involved make it difficult to correlate clustering with functional consequences in vivo. We developed a live-cell super-resolution approach to uncover the correlation between mRNA synthesis and the dynamics of RNA Polymerase II (Pol II) clusters at a gene locus. For endogenous β-actin genes in mouse embryonic fibroblasts, we observe that short-lived (~8 s) Pol II clusters correlate with basal mRNA output. During serum stimulation, a stereotyped increase in Pol II cluster lifetime correlates with a proportionate increase in the number of mRNAs synthesized. Our findings suggest that transient clustering of Pol II may constitute a pre-transcriptional regulatory event that predictably modulates nascent mRNA output.

Keywords: RNA Polymerase II; biophysics; bursting; chromosomes; clustering; gene expression; genes; mRNA; mouse; structural biology; transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / genetics*
  • Animals
  • Cells, Cultured
  • Fibroblasts / physiology
  • Gene Expression Regulation
  • Genetic Loci*
  • Mice
  • RNA Polymerase II / metabolism*
  • RNA, Messenger / biosynthesis*

Substances

  • Actins
  • RNA, Messenger
  • RNA Polymerase II