Chapter category: RNA

Endogenous Substrates of the Yeast NMD Pathway

This chapter appears in the following book:

Nonsense-Mediated mRNA Decay

Edited by: Lynne E. Maquat
ISBN: 1-58706-296-8
» Get more information about this book at landesbioscience.com «

Chapter authors:
Feng He and Allan Jacobson

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The existence of a pathway that promotes rapid decay of nonsense-containing mRNAs raises the question of whether the substrates of this pathway are restricted to aberrant mRNAs. Additional substrates were sought by identifying mRNAs that were selectively stabilized in strains harboring mutations in one or more of the genes encoding factors essential for nonsense-mediated mRNA decay (NMD). These studies have shown that, in addition to standard mRNAs with prematurely terminated open reading frames (ORFs), the substrates of the NMD pathway include: inefficiently spliced pre-mRNAs that enter the cytoplasm with their introns intact, mRNAs in which the ribosome has bypassed the initiator AUG and commenced translation further downstream, some mRNAs containing upstream (u)ORFs, mRNAs subject to frameshifting, bicistronic mRNAs, transcripts of pseudogenes and transposable elements, and mRNAs with abnormal extensions of their 3'-untranslated regions (UTRs). Some of these substrates, e.g., the standard nonsense-containing mRNAs, the intron-containing pre-mRNAs, and the mRNAs derived from pseudogenes can all be considered to be targets of a quality control system seeking to reduce the generation of potentially deleterious polypeptide fragments. However, the existence of other classes of substrates, e.g., mRNAs with uORFs or extended 3'-UTRs, indicates that NMD has additional regulatory capabilities that include the dissociation of aberrant translation termination complexes and the modulation of specific biochemical pathways.

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Chapter category: RNA

Endogenous Substrates of the Yeast NMD Pathway

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