RFX transcription factors are master regulators of ciliogenesis in diverse animal species. The sole Caenorhabditis elegans RFX homolog, DAF-19, plays at least two roles in the formation of functional cilia. The DAF-19(C) isoform is required for ciliogenesis and the DAF-19(M) isoform is required for the functional specialization of a subset of male-specific ciliated neurons called PKD neurons. Here we report the identification of a novel mutation,
daf-19(
sm129), which disrupts the functional specification of PKD neurons and thus suggests that
daf-19m activity is compromised. However, ciliogenesis is not disrupted in
daf-19(
sm129) mutants suggesting that
daf-19c activity is retained. The
sm129 mutation disrupts a splice acceptor site adjacent to an exon common to the
daf-19c and
daf-19m isoforms resulting in aberrant splicing in a proportion of transcripts. While aberrant splicing of
daf-19c to upstream cryptic sites results in in-frame and functional products, a large proportion of
daf-19m mRNAs include the entire upstream intron, which introduces a frameshift and stop codons. At least 15% of disease-causing mutations affect splicing of the gene bearing the mutation, thus it is important to understand the consequences of splice site mutations on gene function. However, predicting the effects of a splice site mutation remains difficult and experimental determination is still required. Using
daf-19(
sm129) as a model, our results suggest that this problem is exacerbated when a splice acceptor mutation is used by multiple isoforms of the same gene because the effects on each isoform can be dramatically different.