The TUTase URT1 connects decapping activators and prevents the accumulation of excessively deadenylated mRNAs to avoid siRNA biogenesis

Nat Commun. 2021 Feb 26;12(1):1298. doi: 10.1038/s41467-021-21382-2.

Abstract

Uridylation is a widespread modification destabilizing eukaryotic mRNAs. Yet, molecular mechanisms underlying TUTase-mediated mRNA degradation remain mostly unresolved. Here, we report that the Arabidopsis TUTase URT1 participates in a molecular network connecting several translational repressors/decapping activators. URT1 directly interacts with DECAPPING 5 (DCP5), the Arabidopsis ortholog of human LSM14 and yeast Scd6, and this interaction connects URT1 to additional decay factors like DDX6/Dhh1-like RNA helicases. Nanopore direct RNA sequencing reveals a global role of URT1 in shaping poly(A) tail length, notably by preventing the accumulation of excessively deadenylated mRNAs. Based on in vitro and in planta data, we propose a model that explains how URT1 could reduce the accumulation of oligo(A)-tailed mRNAs both by favoring their degradation and because 3' terminal uridines intrinsically hinder deadenylation. Importantly, preventing the accumulation of excessively deadenylated mRNAs avoids the biogenesis of illegitimate siRNAs that silence endogenous mRNAs and perturb Arabidopsis growth and development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / genetics
  • Arabidopsis / metabolism*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism*
  • Co-Repressor Proteins / metabolism
  • DEAD-box RNA Helicases / metabolism
  • Gene Expression Regulation, Plant
  • Humans
  • Nicotiana / genetics
  • Proto-Oncogene Proteins / metabolism
  • RNA Nucleotidyltransferases / genetics
  • RNA Nucleotidyltransferases / metabolism*
  • RNA Stability / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism*
  • Ribonucleoproteins / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcriptome
  • Uridine / metabolism

Substances

  • Arabidopsis Proteins
  • Co-Repressor Proteins
  • DCP5 protein, Arabidopsis
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-associated protein 55, human
  • Ribonucleoproteins
  • Saccharomyces cerevisiae Proteins
  • Scd6 protein, S cerevisiae
  • RNA Nucleotidyltransferases
  • URT1 protein, Arabidopsis
  • DDX6 protein, human
  • DHH1 protein, S cerevisiae
  • DEAD-box RNA Helicases
  • Uridine