Global Regulation of miRNA and mRNA Homeostasis by Terminal Uridylyltransferases TENT3A/B
Abstract
The terminal nucleotidyltransferases TENT3A and TENT3B (TENT3A/B) regulate microRNA (miRNA) and messenger RNA (mRNA) stability by 3' end uridylation, leading to degradation by the U-specific exonuclease DIS3L2. Uridylation dependent decay is thought to be a highly specific process, and the prevalence and impact of this pathway on the transcriptome is unexplored. I investigate the prevalence of uridylation dependent decay by transcriptionally profiling HEK 293T cells lacking TENT3A/B. I found while TENT3A/B target a variety of miRNAs, the let-7 family of miRNAs were the most impacted (increased) in TENT3A/B deleted cells. Consequently, let-7 mRNA targets are decreased in abundance in TENT3A/B deleted cells. mRNAs with increased abundance in the deletion strain may be direct targets or TENT3A/B, with transcripts coding for proteins involved in RNA binding, rRNA processing, etc. Finally, the proliferation and adhesion ability of the deletion cells were reduced, indicating the potential of TENT3A/B as cancer treatment targets.