RNA Splicing Promotes Translation and RNA Surveillance

Nat Struct Mol Biol. 2005 Sep;12(9):801-9. doi: 10.1038/nsmb980. Epub 2005 Aug 21.

Abstract

Aberrant mRNAs harboring premature termination codons (PTCs or nonsense codons) are degraded by the nonsense-mediated mRNA decay (NMD) pathway. mRNAs transcribed from genes that naturally acquire PTCs during lymphocyte development are strongly downregulated by PTCs. Here we show that a signal essential for this robust mRNA downregulatory response is efficient RNA splicing. Strong mRNA downregulation can be conferred on a poor NMD substrate by either strengthening its splicing signals or removing its weak introns. Efficient splicing also strongly promotes translation, providing a molecular explanation for enhanced NMD and suggesting that efficient splicing may have evolved to enhance both protein production and RNA surveillance. Our results suggest simple approaches for increasing protein expression from expression vectors and treating human genetic diseases caused by nonsense and frameshift mutations.

Publication types

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

MeSH terms

  • Base Sequence
  • Down-Regulation / genetics
  • Exons / genetics
  • HeLa Cells
  • Humans
  • Introns / genetics
  • Mutation / genetics
  • Protein Biosynthesis / genetics*
  • RNA / genetics*
  • RNA / metabolism*
  • RNA Splice Sites / genetics
  • RNA Splicing / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Transcription, Genetic / genetics

Substances

  • RNA Splice Sites
  • Receptors, Antigen, T-Cell, alpha-beta
  • RNA