A Mettl16/m6A/mybl2b/Igf2bp1 axis ensures cell cycle progression of embryonic hematopoietic stem and progenitor cells
© 2024. The Author(s)..
Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (m6A) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA m6A modification in early embryonic development. Here, using cross-species single-cell RNA sequencing analysis, we found that during early embryonic development, METTL16 is more highly expressed in vertebrate hematopoietic stem and progenitor cells (HSPCs) than other methyltransferases. In Mettl16-deficient zebrafish, proliferation capacity of embryonic HSPCs is compromised due to G1/S cell cycle arrest, an effect whose rescue requires Mettl16 with intact methyltransferase activity. We further identify the cell-cycle transcription factor mybl2b as a directly regulated by Mettl16-mediated m6A modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the m6A reader Igf2bp1 in vivo. Moreover, we found that the METTL16-m6A-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated m6A modification in HSPC cell cycle progression during early embryonic development.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
The EMBO journal - (2024) vom: 11. Apr. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Han, Yunqiao [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Cell Cycle |
|---|
| Anmerkungen: |
Date Revised 11.04.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1038/s44318-024-00082-9 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370945409 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370945409 | ||
| 003 | DE-627 | ||
| 005 | 20240412233937.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240412s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s44318-024-00082-9 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1373.xml |
| 035 | |a (DE-627)NLM370945409 | ||
| 035 | |a (NLM)38605226 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Han, Yunqiao |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A Mettl16/m6A/mybl2b/Igf2bp1 axis ensures cell cycle progression of embryonic hematopoietic stem and progenitor cells |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 11.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (m6A) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA m6A modification in early embryonic development. Here, using cross-species single-cell RNA sequencing analysis, we found that during early embryonic development, METTL16 is more highly expressed in vertebrate hematopoietic stem and progenitor cells (HSPCs) than other methyltransferases. In Mettl16-deficient zebrafish, proliferation capacity of embryonic HSPCs is compromised due to G1/S cell cycle arrest, an effect whose rescue requires Mettl16 with intact methyltransferase activity. We further identify the cell-cycle transcription factor mybl2b as a directly regulated by Mettl16-mediated m6A modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the m6A reader Igf2bp1 in vivo. Moreover, we found that the METTL16-m6A-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated m6A modification in HSPC cell cycle progression during early embryonic development | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a MYBL2 | |
| 650 | 4 | |a Cell Cycle | |
| 650 | 4 | |a Early Embryonic Development | |
| 650 | 4 | |a Hematopoietic Stem and Progenitor Cells (HSPCs) | |
| 650 | 4 | |a METTL16 | |
| 700 | 1 | |a Sun, Kui |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Shanshan |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Yayun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zuxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Jiong |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Hualei |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Liyan |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Manman |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Chaolin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yuwen |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Pan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Xin, Tianqing |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xiaoyan |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Jieping |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Zhaohui |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jianjun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Haojian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xianqin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Mugen |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Daji |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The EMBO journal |d 1982 |g (2024) vom: 11. Apr. |w (DE-627)NLM012617202 |x 1460-2075 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:11 |g month:04 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s44318-024-00082-9 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 11 |c 04 | ||