TENT2, TUT4, and TUT7 selectively regulate miRNA sequence and abundance.
Nat Commun, 2022/09/07;13(1):5260.
Yang A[1], Bofill-De Ros X[1], Stanton R[1], Shao TJ[1, 2], Villanueva P[1], Gu S[3]
Affiliations
PMID: 36071058DOI: 10.1038/s41467-022-32969-8
Impact factor: 17.694
Abstract
TENTs generate miRNA isoforms by 3' tailing. However, little is known about how tailing regulates miRNA function. Here, we generate isogenic HEK293T cell lines in which TENT2, TUT4 and TUT7 are knocked out individually or in combination. Together with rescue experiments, we characterize TENT-specific effects by deep sequencing, Northern blot and in vitro assays. We find that 3' tailing is not random but highly specific. In addition to its known adenylation, TENT2 contributes to guanylation and uridylation on mature miRNAs. TUT4 uridylates most miRNAs whereas TUT7 is dispensable. Removing adenylation has a marginal impact on miRNA levels. By contrast, abolishing uridylation leads to dysregulation of a set of miRNAs. Besides let-7, miR-181b and miR-222 are negatively regulated by TUT4/7 via distinct mechanisms while the miR-888 cluster is upregulated specifically by TUT7. Our results uncover the selective actions of TENTs in generating 3' isomiRs and pave the way to investigate their functions.
MeSH terms
DNA-Binding Proteins; HEK293 Cells; Humans; MicroRNAs; Polynucleotide Adenylyltransferase; RNA Nucleotidyltransferases; Uridine Monophosphate; mRNA Cleavage and Polyadenylation Factors
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download