RNA-methyltransferase Nsun5 controls the maternal-to-zygotic transition by regulating maternal mRNA stability
© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics..
BACKGROUND: RNA 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.
METHODS: Mouse 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.
RESULTS: Here, 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.
CONCLUSIONS: Nsun5 loss arrests follicular genesis and development in ovarian aging, indicating that Nsun5/m5 C-regulated maternal mRNA stabilization is essential for MZT transition.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Clinical and translational medicine - 12(2022), 12 vom: 10. Dez., Seite e1137 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ding, Chenyue [VerfasserIn] |
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| Links: |
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| Themen: |
63231-63-0 |
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| Anmerkungen: |
Date Completed 16.12.2022 Date Revised 26.01.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/ctm2.1137 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM350073368 |
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| 245 | 1 | 0 | |a RNA-methyltransferase Nsun5 controls the maternal-to-zygotic transition by regulating maternal mRNA stability |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. | ||
| 520 | |a BACKGROUND: RNA 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 | ||
| 520 | |a METHODS: Mouse 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 | ||
| 520 | |a RESULTS: Here, 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 | ||
| 520 | |a CONCLUSIONS: Nsun5 loss arrests follicular genesis and development in ovarian aging, indicating that Nsun5/m5 C-regulated maternal mRNA stabilization is essential for MZT transition | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Lu, Jiafeng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jincheng |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Xiujuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhenxing |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Han |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Boxian |e verfasserin |4 aut | |
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