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

Abstract

A fundamental principle in biology is that the program for early development is established during oogenesis in the form of the maternal transcriptome1,2. How the maternal transcriptome acquires the appropriate content and dosage of transcripts is not fully understood. Here we show that TUT4/7-mediated mRNA 3′ terminal uridylation sculpts the mouse maternal transcriptome by eliminating transcripts during oocyte growth. TUT4/7-mediated uridylation is essential for both oocyte maturation and fertility. In comparison to somatic cells, the oocyte transcriptome displays shorter poly(A) tail length and a high relative proportion of terminal oligo-uridylation. TUT4/7 deletion 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. In contrast, TUT4/7-deficiency does not alter gene expression in a variety of somatic cells. In summary, we show essential and specific functions for poly(A) tail length and 3′ terminal uridylation in sculpting a functional maternal transcriptome.

Terminal Uridylyltransferases Execute Programmed Clearance of Maternal Transcriptome in Vertebrate Embryos

“…We also observed that TUT4/7 knockdown partially blocks the increase of uridylation during Xenopus oocyte maturation ( Figures S4A and S4B). Thus, TUT4 and/or TUT7 are responsible for mRNA uridylation in fish and frog, as well as in mammals Morgan et al, 2017). Conversely, the splicing-blocking morpholinos had no detectable effect during these stages (data not shown), which is consistent with a previous report (Thornton et al, 2014).…”

Cyclin B2 is required for progression through meiosis in mouse oocytes

“…However, although little Ccnb1 mRNA loading onto ribosomes was detected in GV-arrested oocytes, Ccnb2 mRNA loading was considerably higher. These indirect measures of translation were corroborated by mining data sets assessing the poly(A)-tail length of mRNAs in GV-arrested oocytes (Morgan et al, 2017). Ccnb2 mRNA had a significantly longer poly(A)-tail compared with Ccnb1 (Fig.…”

The role of 3′ end uridylation in RNA metabolism and cellular physiology

“…Several recent studies demonstrated that uridylation is a key factor in germline development, early embryogenesis and differentiation [30,74]. The expression of TUT4/7 is elevated during embryogenesis, which indicates their importance in development.…”

“…The expression of TUT4/7 is elevated during embryogenesis, which indicates their importance in development. TUT4/7 play a major role in the establishment of the mammalian maternal transcriptome during oogenesis [30]. Each stage of oogenesis expresses a specific transcriptome.…”

“…Oocytes need to have the ability to selectively degrade mRNAs that are specific to the previous stage. This selective removal is regulated by deadenylation and uridylation [30]. The uridylation activities of TUT4 and TUT7 are required to mediate the selective removal of mRNA pools with short poly(A)-tails in several stages during oogenesis.…”