Nonsense-Mediated mRNA Decay: A Comparative Analysis of Different Species

L.   E.   Maquat

Abstract

Nonsense-mediated mRNA decay (NMD) functions to ensure quality gene expression by degrading mRNAs that prematurely terminate translation. By so doing, it eliminates the production of potentially deleterious truncated proteins. NMD also degrades certain naturally occurring transcripts as a means of achieving proper levels of gene expression. With the exception of prokaryotes, NMD typifies all organisms that have been examined. As an example of its importance, NMD is required for the viability of mammalian blastocysts in culture as well as mammalian embryos in utero. The repertoire of factors that mediate NMD is larger in C. elegans, D. melanogaster, mammalian cells and, possibly, A. thaliana, than it is in S. cerevisiae and S. pombe. NMD requires not only a premature termination codon but also a downstream element. Whereas this element in S. cerevisiae, S. pombe, C. elegans, D. melanogaster and plants is debatably either a short cis-acting mRNA sequence or an abnormal 3 untranslated region, it is a splicing-generated exon junction complex of proteins in mammalian cells. In fact, NMD may have provided a selective pressure for where introns colonize within mammalian genes. There also appear to be differences among different eukaryotes as to whether NMD is restricted to newly synthesized mRNA or can also target steady-state mRNA. In summary, despite the conservation of NMD in eukaryotes, different mechanisms have evolved to define those premature termination codons that elicit NMD.

Keywords: nonsense-mediated mrna decay, rna surveillance, premature termination of translation, upf proteins