mRNA 3' uridylation and poly(A) tail length sculpt the mammalian maternal transcriptome

Nature. 2017 Aug 17;548(7667):347-351. doi: 10.1038/nature23318. Epub 2017 Aug 9.

Abstract

A fundamental principle in biology is that the program for early development is established during oogenesis in the form of the maternal transcriptome. How the maternal transcriptome acquires the appropriate content and dosage of transcripts is not fully understood. Here we show that 3' terminal uridylation of mRNA mediated by TUT4 and TUT7 sculpts the mouse maternal transcriptome by eliminating transcripts during oocyte growth. Uridylation mediated by TUT4 and TUT7 is essential for both oocyte maturation and fertility. In comparison to somatic cells, the oocyte transcriptome has a shorter poly(A) tail and a higher relative proportion of terminal oligo-uridylation. Deletion of TUT4 and TUT7 leads to the accumulation of a cohort of transcripts with a high frequency of very short poly(A) tails, and a loss of 3' oligo-uridylation. By contrast, deficiency of TUT4 and TUT7 does not alter gene expression in a variety of somatic cells. In summary, we show that poly(A) tail length and 3' terminal uridylation have essential and specific functions in shaping a functional maternal transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • Female
  • Infertility, Female / genetics
  • Male
  • Maternal Inheritance / genetics*
  • Mice
  • Mice, Knockout
  • Mothers
  • Nucleotidyltransferases / deficiency
  • Nucleotidyltransferases / genetics
  • Oocytes / growth & development
  • Oocytes / metabolism*
  • Organ Specificity
  • Poly A / chemistry
  • Poly A / metabolism*
  • RNA Stability
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism*
  • Transcriptome*
  • Uridine Monophosphate / metabolism*

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • Poly A
  • Uridine Monophosphate
  • Nucleotidyltransferases
  • ZCCHC11 protein, mouse
  • terminal uridylyl transferase 7, mouse