Splicing Removes the Caenorhabditis elegans Transposon Tc1 from Most Mutant Pre-mRNAs

Abstract

The transposable element Tc1 is responsible for most spontaneous mutations that occur in many Caenorhabditis elegans strains. We analyzed the abundance and sequence of mRNAs expressed from five different Tc1 insertions within either hlh-1 (a MyoD homolog) or unc-54 (a myosin heavy chain gene). Each of the mutants expresses substantial quantities of mature mRNA in which most or all of Tc1 has been removed by splicing. Such mRNAs contain small insertions of Tc1 sequences and/or deletions of target gene sequences at the resulting spliced junctions. Most of these mutant mRNAs do not contain premature stop codons, and many are translated in frame to produce proteins that are functional in vivo. The number and variety of splice sites used to remove Tc1 from these mutant pre-mRNAs are remarkable. Two-thirds of the Tc1-containing introns removed from hlh-1 and unc-54 lack either the 5'-GU or AG-3' dinucleotides typically found at the termini of eukaryotic introns. We conclude that splicing to remove Tc1 from mutant pre-mRNAs allows many Tc1 insertions to be phenotypically silent. Such mRNA processing may help Tc1 escape negative selection.