RNA polymerase II CTD S2P is dispensable for embryogenesis but mediates exit from developmental diapause in <i>C. elegans</i>.

Abstract

Serine 2 phosphorylation (S2P) within the CTD of RNA polymerase II is considered a Cdk9/Cdk12-dependent mark required for 3'-end processing. However, the relevance of CTD S2P in metazoan development is unknown. We show that <i>cdk-12</i> lesions or a full-length CTD S2A substitution results in an identical phenotype in <i>Caenorhabditis elegans</i> Embryogenesis occurs in the complete absence of S2P, but the hatched larvae arrest development, mimicking the diapause induced when hatching occurs in the absence of food. Genome-wide analyses indicate that when CTD S2P is inhibited, only a subset of growth-related genes is not properly expressed. These genes correspond to SL2 trans-spliced mRNAs located in position 2 and over within operons. We show that CDK-12 is required for maximal occupancy of cleavage stimulatory factor necessary for SL2 trans-splicing. We propose that CTD S2P functions as a gene-specific signaling mark ensuring the nutritional control of the <i>C. elegans</i> developmental program.