Temperature regulates splicing efficiency of the cold-inducible RNA-binding protein gene Cirbp

Genes Dev. 2016 Sep 1;30(17):2005-17. doi: 10.1101/gad.287094.116. Epub 2016 Sep 15.

Abstract

In mammals, body temperature fluctuates diurnally around a mean value of 36°C-37°C. Despite the small differences between minimal and maximal values, body temperature rhythms can drive robust cycles in gene expression in cultured cells and, likely, animals. Here we studied the mechanisms responsible for the temperature-dependent expression of cold-inducible RNA-binding protein (CIRBP). In NIH3T3 fibroblasts exposed to simulated mouse body temperature cycles, Cirbp mRNA oscillates about threefold in abundance, as it does in mouse livers. This daily mRNA accumulation cycle is directly controlled by temperature oscillations and does not depend on the cells' circadian clocks. Here we show that the temperature-dependent accumulation of Cirbp mRNA is controlled primarily by the regulation of splicing efficiency, defined as the fraction of Cirbp pre-mRNA processed into mature mRNA. As revealed by genome-wide "approach to steady-state" kinetics, this post-transcriptional mechanism is widespread in the temperature-dependent control of gene expression.

Keywords: Cirbp; circadian rhythms; splicing efficiency; temperature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Temperature
  • Cold Temperature
  • Gene Expression Regulation*
  • Genome-Wide Association Study
  • Liver / metabolism
  • Mice
  • NIH 3T3 Cells
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Splicing / physiology*
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • RNA Processing, Post-Transcriptional
  • RNA Stability / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*
  • Temperature*

Substances

  • Cirbp protein, mouse
  • Protein Isoforms
  • RNA Precursors
  • RNA, Messenger
  • RNA-Binding Proteins