Maternal mRNA deadenylation and allocation via Rbm14 condensates facilitate vertebrate blastula development

Abstract

Early embryonic development depends on proper utilization and clearance of maternal transcriptomes. How these processes are spatiotemporally regulated remains unclear. Here we show that nuclear RNA‐binding protein Rbm14 and maternal mRNAs co‐phase separate into cytoplasmic condensates to facilitate vertebrate blastula‐to‐gastrula development. In zebrafish, Rbm14 condensates were highly abundant in blastomeres and markedly reduced after prominent activation of zygotic transcription. They concentrated at spindle poles by associating with centrosomal γ‐tubulin puncta and displayed mainly asymmetric divisions with a global symmetry across embryonic midline in 8‐ and 16‐cell embryos. Their formation was dose‐dependently stimulated by m6A, but repressed by m5C modification of the maternal mRNA. Furthermore, deadenylase Parn co‐phase separated with these condensates, and this was required for deadenylation of the mRNAs in early blastomeres. Depletion of Rbm14 impaired embryonic cell differentiations and full activations of the zygotic genome in both zebrafish and mouse and resulted in developmental arrest at the blastula stage. Our results suggest that cytoplasmic Rbm14 condensate formation regulates early embryogenesis by facilitating deadenylation, protection, and mitotic allocation of m6A‐modified maternal mRNAs, and by releasing the poly(A)‐less transcripts upon regulated disassembly to allow their re‐polyadenylation and translation or clearance.

The molecular mechanisms underpinning maternal mRNA dormancy

“…It is important to note that the mechanisms described do not operate in isolation. For example, RNA modifications can affect RNA granule formation [ 74 ], and proteins that interfere with eIF4F assembly or binding to the mRNA cap can sense the length of the polyA tail at the 3′ end (e.g. eIF4E1b binds to mRNAs with reported short polyA tails [ 86 ]).…”

“…Furthermore, m 6 A and m 5 C have been proposed to play opposing roles in the formation of cytoplasmic condensates containing maternal mRNAs, the RNA-binding protein Rbm14 and the deadenylase PARN. While m 6 A promoted condensate formation and PARN activity, m 5 C antagonized it [ 74 ]. Investigating how m 6 A and m 5 C modifications are specifically deposited will be key to understanding their effects on translation and mRNA stability during development.…”

RNA m5C methylation modification: a potential therapeutic target for SARS-CoV-2-associated myocarditis

“…This dynamically reversible modification is catalytically generated by methyltransferases, removed by demethylases, and recognized by specific readers. On the other hand, m5C is also involved in regulating many physiological and pathological processes such as embryonic development ( 19 , 23 , 24 ), tumor development ( 25 , 26 ), viral replication ( 22 , 27 ), and stem cell differentiation ( 28 – 31 ) ( Figure 1 ).…”