An apparent pseudo-exon acts both as an alternative exon that leads to nonsense-mediated decay and as a zero-length exon

Mol Cell Biol. 2006 Mar;26(6):2237-46. doi: 10.1128/MCB.26.6.2237-2246.2006.

Abstract

Pseudo-exons are intronic sequences that are flanked by apparent consensus splice sites but that are not observed in spliced mRNAs. Pseudo-exons are often difficult to activate by mutation and have typically been viewed as a conceptual challenge to our understanding of how the spliceosome discriminates between authentic and cryptic splice sites. We have analyzed an apparent pseudo-exon located downstream of mutually exclusive exons 2 and 3 of the rat alpha-tropomyosin (TM) gene. The TM pseudo-exon is conserved among mammals and has a conserved profile of predicted splicing enhancers and silencers that is more typical of a genuine exon than a pseudo-exon. Splicing of the pseudo-exon is fully activated for splicing to exon 3 by a number of simple mutations. Splicing of the pseudo-exon to exon 3 is predicted to lead to nonsense-mediated decay (NMD). In contrast, when "prespliced" to exon 2 it follows a "zero length exon" splicing pathway in which a newly generated 5' splice site at the junction with exon 2 is spliced to exon 4. We propose that a subset of apparent pseudo-exons, as exemplified here, are actually authentic alternative exons whose inclusion leads to NMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Codon, Nonsense
  • Conserved Sequence
  • Exons*
  • Gene Expression Regulation
  • Humans
  • Molecular Sequence Data
  • Point Mutation
  • Pseudogenes*
  • RNA Stability*
  • Rats
  • Tropomyosin / genetics
  • Tropomyosin / metabolism

Substances

  • Codon, Nonsense
  • Tropomyosin