THE MEC-8 GENE OF CAENORHABDITIS-ELEGANS ENCODES A PROTEIN WITH 2 RNARECOGNITION MOTIFS AND REGULATES ALTERNATIVE SPLICING OF UNC-52 TRANSCRIPTS

Mutations in the mec-8 gene of Caenorhabditis elegans were previously shown to affect the functions of body wall muscle and mechanosensory a nd chemosensory neurons, Mutations in mec-8 also strongly enhance the mutant phenotype of specific mutations in unc-52, a gene that encodes, via alternative splicing of pre-mRNA, a set of basement membrane prot eins, homologs of perlecan, that are important for body wall muscle as sembly and attachment to basement membrane, hypodermis and cuticle, We have cloned mec-8 and found that it encodes a protein with two RNA re cognition motifs, characteristic of RNA binding proteins, We have used reverse transcription-PCR and RNase protection experiments to show th at mec-8 regulates the accumulation of a specific subset of alternativ ely spliced unc-52 transcripts, We have also shown with antibodies to UNC-52 that mec-8 affects the abundance of a subset of UNC-52 isoforms . We propose that mec-8 encodes a trans-acting factor that regulates t he alternative splicing of the pre-mRNA of unc-52 and one or more addi tional genes that affect mechanosensory and chemosensory neuron functi on.