RNA splicing regulates the temporal order of TNF-induced gene expression

Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11934-9. doi: 10.1073/pnas.1309990110. Epub 2013 Jun 28.

Abstract

When cells are induced to express inflammatory genes by treatment with TNF, the mRNAs for the induced genes appear in three distinct waves, defining gene groups I, II, and III, or early, intermediate, and late genes. To examine the basis for these different kinetic classes, we have developed a PCR-based procedure to distinguish pre-mRNAs from mRNAs. It shows that the three groups initiate transcription virtually simultaneously but that delays in splicing characterize groups II and III. We also examined the elongation times, concluding that pre-mRNA synthesis is coordinate but splicing differences directly regulate the timing of mRNA production.

Keywords: NF-κB; gene regulation; gene transcription; inflammation.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / physiology*
  • Humans
  • Kinetics
  • Mice
  • RNA Precursors / genetics*
  • RNA Splicing / genetics
  • RNA Splicing / physiology*
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction / methods
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • RNA Precursors
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha