Trends in Biochemical Sciences
A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance
Section snippets
Distinguishing termination codons that reduce mRNA abundance from those that do not
The discovery of nonsense-mediated safeguard mechanisms raises a question: what distinguishes a normal termination codon (which does not generally elicit a reduction in mRNA abundance) from a premature termination codon (which generally does elicit a reduction in mRNA abundance)? In mammalian cells, the distinction between the two appears to lie neither in the sequence of the termination codon (UAA, UAG or UGA) nor in the nucleotides that flank the termination codon, but rather in the position
Testing the rule for termination-codon position
The normal termination codon of most intron-containing genes resides within the last exon[13], which is consistent with the rule for termination-codon position. However, we imagined that a particularly revealing test of the rule would be an analysis of genes that possess one or more 3′-untranslated exons. Therefore, we undertook an exhaustive survey of genes of this type from a variety of organisms, including fungi, plants, insects and vertebrates. Only 7% of the 1500 genes surveyed were found
Significance of the rule for termination-codon position
The rule for termination-codon position has broad implications given that, in principle, any intron located more than 50–55 nucleotides downstream of a termination codon could mediate a reduction in mRNA abundance. For example, the rule predicts that insertion of an intron more than 50–55 nucleotides downstream of a normal termination codon should elicit a reduction in mRNA abundance. In fact, this has been shown for the β-globin gene, and mutation of the normal β-globin termination codon so
Acknowledgements
This work was supported by Public Health Service research grants from the NIH to L. E. M. (grant numbers DK33933 and GM52822). We thank Tamás Henics for drawing the cartoon.
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