Unproductively spliced ribosomal protein mRNAs are natural targets of mRNAsurveillance in C-elegans

Messenger RNA surveillance, the selective and rapid degradation of mRNAs co ntaining premature stop codons, occurs in all eukaryotes tested. The biolog ical role of this decay pathway, however, is not well understood. To identi fy natural substrates of mRNA surveillance, we used a cDNA-based representa tional difference analysis to identify mRNAs whose abundance increases in C aenorhabditis elegans smg(-) mutants, which are deficient for mRNA surveill ance. 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, w hose abundance does not change in smg(-) mutants, encodes a normal, full-le ngth, ribosomal protein. An unproductively spliced mRNA, whose abundance in creases dramatically in smg(-) mutants, contains premature stop codons beca use 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 appear s to autoregulate its own splicing, with unproductively spliced mRNAs being degraded by mRNA surveillance. We demonstrate further that alternative spl icing of rpl introns is conserved among widely diverged nematodes. Our resu lts suggest that one important role of mRNA surveillance is to eliminate un productive by-products of gene regulation.