Dataset Information

Reading and writing of mRNA m⁶A modification orchestrate maternal-to-zygotic transition in mice.

ABSTRACT: N⁶-methyladenosine (m⁶A) modification has been shown to regulate RNA metabolism. Here, we investigate m⁶A dynamics during maternal-to-zygotic transition (MZT) in mice through multi-omic analysis. Our results show that m⁶A can be maternally inherited or de novo gained after fertilization. Interestingly, m⁶A modification on maternal mRNAs not only correlates with mRNA degradation, but also maintains the stability of a small group of mRNAs thereby promoting their translation after fertilization. We identify Ythdc1 and Ythdf2 as key m⁶A readers for mouse preimplantation development. Our study reveals a key role of m⁶A mediated RNA metabolism during MZT in mammals.

SUBMITTER: Zhu W

PROVIDER: S-EPMC10080794 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Reading and writing of mRNA m6A modification orchestrate maternal-to-zygotic transition in mice.

Zhu Wencheng W Ding Yufeng Y Meng Juan J Gu Lei L Liu Wenjun W Li Li L Chen Hongyu H Wang Yining Y Li Ziyi Z Li Chen C Sun Yidi Y Liu Zhen Z

Genome biology 20230406 1

N6-methyladenosine (m6A) modification has been shown to regulate RNA metabolism. Here, we investigate m6A dynamics during maternal-to-zygotic transition (MZT) in mice through multi-omic analysis. Our results show that m6A can be maternally inherited or de novo gained after fertilization. Interestingly, m6A modification on maternal mRNAs not only correlates with mRNA degradation, but also maintains the stability of a small group of mRNAs ther ...[more]

PMID: 37024923

Similar Datasets

Project description:BackgroundRNA modification-induced ovarian dysgenesis appears to be necessary for ovary development. However, how m5 C (5-methylcytosine)-coordinating modificatory transcripts are dynamically regulated during oogenesis, and ovarian development is unknown. The purpose of this study was to determine whether NOP2/Sun RNA methyltransferase 5 (Nsun5) deletion leads to suppression of ovarian function and arrest of embryonic development. The regulation of mRNA decay and stability by m5 C modification is essential at multiple stages during the maternal-to-zygotic (MZT) transition.MethodsMouse ovaries and oocytes with Nsun5KO and the KGN cell line were subjected to m5 C identification, alternative splicing analysis and protein expression. BS-m5 C-seq, real-time polymerase chain reaction, Western blot, immunofluorescence and actinomycin D treatment assays were used. In particular, BS-m5 C-seq revealed a dynamic pattern of m5 C sites and genes in the ovaries between Nsun5KO and WT mice at the 2-month and 6-month stages. Diverse bioinformatic tools were employed to identify target genes for Nsun5.ResultsHere, a maternal mRNA stability study showed that deletion of the m5 C methyltransferase Nsun5 obstructs follicular development and ovarian function, which leads directly to inhibition of embryogenesis and embryo development. Dynamic analysis of m5 C revealed that the level of m5 C decreased in a time-dependent manner after Nsun5 knockout. Regarding the molecular mechanism, we found that Nsun5 deficiency caused a m5 C decline in the exon and 3'UTR regions that influenced the translation efficiency of Mitotic arrest deficient 2 like 2 (MAD2L2) and Growth differentiation factor 9 (GDF9) in the ovary. Mechanistic investigation of alternative splicing indicated that Nsun5KO triggers aberrant events in the exon region of Brd8.ConclusionsNsun5 loss arrests follicular genesis and development in ovarian aging, indicating that Nsun5/m5 C-regulated maternal mRNA stabilization is essential for MZT transition.

Dataset Information

Reading and writing of mRNA m⁶A modification orchestrate maternal-to-zygotic transition in mice.

Publications

Reading and writing of mRNA m<sup>6</sup>A modification orchestrate maternal-to-zygotic transition in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets