Terminal Uridylyltransferases Execute Programmed Clearance of Maternal Transcriptome in Vertebrate Embryos

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.

The maternal-to-zygotic transition revisited

“…)* (Bazzini et al, 2016) Not studied during the MZT D. rerio ∼70% (Aanes et al, 2011;Harvey et al, 2013) YBX1 (Sun et al, 2018) >25% (Aanes et al, 2011;Harvey et al, 2013;Mishima and Tomari, 2016) hnRNPA* (Despic et al, 2017) PUM* (Rabani et al, 2017) ARE-BP* (Rabani et al, 2017) miR-430 (Bazzini et al, 2012;Giraldez et al, 2006) Yes (DDX6?) (Bazzini et al, 2016;Mishima and Tomari, 2016) N 6 -methyladenosine (Zhao et al, 2017) Terminal uridylation (Chang et al, 2018) Xenopus Not studied FRGY2 (X. laevis) (Bouvet and Wolffe, 1994;Matsumoto et al, 1996) Not studied ARE-BP (X. laevis) (Voeltz and Steitz, 1998;Moraes et al, 2006) miR-427 (X. laevis) (Lund et al, 2009) Yes (DDX6? )* (X. laevis) (Bazzini et al, 2016) Terminal uri...…”

Igf2bp3 maintains maternal RNA stability and ensures early embryo development in zebrafish

“…mRNA stability is usually modulated by their 5′ cap and 3′ poly (A) tail length 9,10 . Recently, N6-methyladenosine (m 6 A), the most prevalent modification in eukaryotic mRNA, has been correlated with mRNA stability.…”

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.…”

“…Uridylation further regulates events after fertilization via targeting coding [74] as well as ncRNAs [107,108]. The early zygote is transcriptionally inactive and its gene expression is ruled by the maternal transcriptome pool of the oocyte, which is formed during folliculogenesis [109,110].…”

“…The critical step in MTZ is an efficient and specific removal of maternal mRNAs. A genome-wide study revealed that the clearance of maternal mRNA is also facilitated by TUT4/7 uridylation and that uridylation is necessary for early embryo development [74]. Altogether, mRNA uridylation is a key component in shaping the maternal transcriptome and in its subsequent removal, and in turn, in the regulation of proper embryogenesis.…”