ORIGIN, PROPERTIES, AND REGULATED EXPRESSION OF MULTIPLE MESSENGER-RNAS ENCODED BY THE PROTEIN-KINASE C1 GENE OF CAENORHABDITIS-ELEGANS

Recently, we cloned and characterized cDNA encoding a novel, protein k inase C (designated PKC1B) from Caenorhabditis elegans. PKC1B (707 ami no acid residues) is a developmentally regulated, calcium-independent kinase that is expressed exclusively in sensory neurons and related in terneurons. We have now discovered a mechanism by which a second, dist inct mRNA (PKC1A mRNA) with increased protein coding potential is gene rated from the C. elegans PKC1 gene. PKC1A mRNA is produced in a proce ss that involves the utilization of an alternative, distal promoter, t he incorporation of two unique exons into the mRNA, and alternative ci s/trans splicing. Diversity among PKC1 gene transcripts is increased s ubstantially by trans-splicing. The 5' end of PKC1A mRNA contains an a cceptor site that is modified by the addition of either a classical sp liced leader sequence 2 or one of four novel spliced leaders. PKC1A mR NA encodes a predicted kinase that contains the entire sequence of PKC 1B as well as an N-terminal extension of 56 residues. The extension co ntains a preponderance of basic amino acids. The levels of transcripts arising from the distal (1A) and proximal (1B) promoters for the PKC1 gene are differentially regulated during C. elegans development. The ratio of 1B mRNA:1A mRNA varies from 40:1 to unity as the nematodes pr ogress from early larval stages to mature adults. The novel exons in t he PKC1A structural gene are not contiguous with the PKC1A promoter bu t are instead positioned downstream from a second gene, kinase upstrea m gene-1, in the context of a multicistronic operon. PKC1A and kinase upstream gene-1 mRNAs are coordinately expressed in a fixed ratio thro ughout C. elegans post-embryonic development, suggesting that a shared upstream promoter regulates transcription of both genes. Finally, PKC 1A and PKC1B mRNA levels are differentially regulated by phorbol ester s in a process that may involve the participation of another PKC isofo rm that is analogous to mammalian PKC delta.