The SSUP-72/PINN-1 module is required for efficient 3’end processing and coordinates developmental gene expression during exit from diapause in C. elegans [GROseq]

During the exit from the developmental diapause of Caenorhabditis elegans (C. elegans), a network of growth and developmental genes is activated. These genes are organized into operons, where transcriptional termination is uncoupled from mRNA 3’-end processing. Although the Pol II CTD-S2P mark deposited by CDK-12 is unnecessary during embryogenesis, it plays a critical role in the timely expression of most operonic genes by enhancing SL2 trans-splicing at position 2 and above. This process protects mRNA from degradation and prevents termination. Here, a genetic screen has identified the SSUP-72/PINN-1 module as an effective suppressor of CDK-12-induced defects. Our data show that the SSUP-72/PINN-1 module regulates intra-operon termination and affects 3’ pausing genome-wide, coordinating growth and developmental gene expression during post-embryonic development in C. elegans. Global Run-On sequencing (GRO-seq) for CDK-12as (analogue-sensitive) and its suppressive mutation ssup-72[E22K]. Worms were L1 synchronized by hypochlorite treatment and grown 4H in presence of 3MB-PP1 (2 uM) prior to nuclei extraction.