Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans

AUTOR(ES)

Lewis, Benjamin P.

FONTE

The National Academy of Sciences

RESUMO

To better understand the role of alternative splicing, we conducted a large-scale analysis of reliable alternative isoforms of known human genes. Each isoform was classified according to its splice pattern and supporting evidence. We found that one-third of the alternative transcripts examined contain premature termination codons, and most persist even after rigorous filtering by multiple methods. These transcripts are apparent targets of nonsense-mediated mRNA decay (NMD), a surveillance mechanism that selectively degrades nonsense mRNAs. Several of these transcripts are from genes for which alternative splicing is known to regulate protein expression by generating alternate isoforms that are differentially subjected to NMD. We propose that regulated unproductive splicing and translation (RUST), through the coupling of alternative splicing and NMD, may be a pervasive, underappreciated means of regulating protein expression.

Documentos Relacionados

• Nonsense-Mediated Decay of Human HEXA mRNA
• Nonsense-mediated mRNA decay mutes the splicing defects of spliceosome component mutations
• Nonsense-Mediated Decay of Mutant waxy mRNA in Rice
• Killing the messenger: new insights into nonsense-mediated mRNA decay
• Integration of splicing, transport and translation to achieve mRNA quality control by the nonsense-mediated decay pathway