Terminal Uridylyltransferases Execute Programmed Clearance of Maternal Transcriptome in Vertebrate Embryos

Mol Cell. 2018 Apr 5;70(1):72-82.e7. doi: 10.1016/j.molcel.2018.03.004.

Abstract

During the maternal-to-zygotic transition (MZT), maternal RNAs are actively degraded and replaced by newly synthesized zygotic transcripts in a highly coordinated manner. However, it remains largely unknown how maternal mRNA decay is triggered in early vertebrate embryos. Here, through genome-wide profiling of RNA abundance and 3' modification, we show that uridylation is induced at the onset of maternal mRNA clearance. The temporal control of uridylation is conserved in vertebrates. When the homologs of terminal uridylyltransferases TUT4 and TUT7 (TUT4/7) are depleted in zebrafish and Xenopus, maternal mRNA clearance is significantly delayed, leading to developmental defects during gastrulation. Short-tailed mRNAs are selectively uridylated by TUT4/7, with the highly uridylated transcripts degraded faster during the MZT than those with unmodified poly(A) tails. Our study demonstrates that uridylation plays a crucial role in timely mRNA degradation, thereby allowing the progression of early development.

Keywords: RNA decay; TAIL-seq; TUT4; TUT7; U tail; Zcchc11; Zcchc6; maternal-to-zygotic transition; poly(A) tail; uridylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics
  • Embryo, Mammalian / enzymology*
  • Embryo, Nonmammalian / enzymology*
  • Gastrulation
  • Gene Expression Regulation, Developmental
  • Gestational Age
  • Mice, Inbred ICR
  • Nucleotidyltransferases / genetics
  • Nucleotidyltransferases / metabolism*
  • RNA Processing, Post-Transcriptional
  • RNA Stability*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Transcriptome*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics*
  • Xenopus laevis / metabolism
  • Zebrafish / embryology
  • Zebrafish / genetics*
  • Zebrafish / metabolism

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • Xenopus Proteins
  • Nucleotidyltransferases
  • TUT7 protein, Xenopus
  • ZCCHC11 protein, mouse
  • terminal uridylyl transferase 7, mouse