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Vol. 14, No. 17, pp. 2173-2184, September 1, 2000
Department of Genetics, University of Wisconsin, Madison, Wisconsin
53706 USA
Messenger RNA surveillance, the selective and rapid degradation of
mRNAs containing premature stop codons, occurs in all eukaryotes tested. The biological role of this decay pathway, however, is not well
understood. To identify natural substrates of mRNA surveillance, we
used a cDNA-based representational difference analysis to identify mRNAs whose abundance increases in Caenorhabditis elegans
smg(
) mutants, which are deficient for mRNA surveillance.
Alternatively spliced mRNAs of genes encoding ribosomal proteins L3,
L7a, L10a, and L12 are abundant natural targets of mRNA surveillance.
Each of these genes expresses two distinct mRNAs. A productively
spliced mRNA, whose abundance does not change in smg()
mutants, encodes a normal, full-length, ribosomal protein. An
unproductively spliced mRNA, whose abundance increases dramatically in
smg() mutants, contains premature stop codons because of
incomplete removal of an alternatively spliced intron. In transgenic
animals expressing elevated quantities of RPL-12, a greater proportion
of endogenous rpl-12 transcript is spliced unproductively.
Thus, RPL-12 appears to autoregulate its own splicing, with
unproductively spliced mRNAs being degraded by mRNA surveillance. We
demonstrate further that alternative splicing of rpl introns is
conserved among widely diverged nematodes. Our results suggest that one
important role of mRNA surveillance is to eliminate unproductive
by-products of gene regulation.
[Key Words: mRNA surveillance; ribosomal protein autoregulation; regulated alternative splicing]
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