Identification of Germ Cell-specific Mga Variant MRNA That Promotes Meiosis Via Impediment of a Non-canonical PRC1

Overview

Journal Sci Rep

Specialty Science

Date 2021 May 7

PMID 33958653

Citations 7

Authors

Yuka Kitamura

Kousuke Uranishi

Masataka Hirasaki

Masazumi Nishimoto

Ayumu Suzuki

Akihiko Okuda

Affiliations

Soon will be listed here.

Abstract

A non-canonical PRC1 (PRC1.6) prevents precocious meiotic onset. Germ cells alleviate its negative effect by reducing their amount of MAX, a component of PRC1.6, as a prerequisite for their bona fide meiosis. Here, we found that germ cells produced Mga variant mRNA bearing a premature termination codon (PTC) during meiosis as an additional mechanism to impede the function of PRC1.6. The variant mRNA encodes an anomalous MGA protein that lacks the bHLHZ domain and thus functions as a dominant negative regulator of PRC1.6. Notwithstanding the presence of PTC, the Mga variant mRNA are rather stably present in spermatocytes and spermatids due to their intrinsic inefficient background of nonsense-mediated mRNA decay. Thus, our data indicate that meiosis is controlled in a multi-layered manner in which both MAX and MGA, which constitute the core of PRC1.6, are at least used as targets to deteriorate the integrity of the complex to ensure progression of meiosis.

Citing Articles

Female-specific mechanisms of meiotic initiation and progression in mammalian oocyte development.

Shimada R, Ishiguro K Genes Cells. 2024; 29(10):797-807.

PMID: 39119753 PMC: 11555627. DOI: 10.1111/gtc.13152.

Destabilization of mRNAs enhances competence to initiate meiosis in mouse spermatogenic cells.

Pfaltzgraff N, Liu B, de Rooij D, Page D, Mikedis M Development. 2024; 151(14).

PMID: 38884383 PMC: 11273298. DOI: 10.1242/dev.202740.

Identification of genetic variants affecting reproduction traits in Vrindavani cattle.

Gangwar M, Kumar S, Ahmad S, Singh A, Agrawal S, Anitta P Mamm Genome. 2023; 35(1):99-111.

PMID: 37924370 DOI: 10.1007/s00335-023-10023-2.

SMG6 localizes to the chromatoid body and shapes the male germ cell transcriptome to drive spermatogenesis.

Lehtiniemi T, Bourgery M, Ma L, Ahmedani A, Makela M, Asteljoki J Nucleic Acids Res. 2022; 50(20):11470-11491.

PMID: 36259644 PMC: 9723633. DOI: 10.1093/nar/gkac900.

PFOA-Induced Ovotoxicity Differs Between Lean and Obese Mice With Impacts on Ovarian Reproductive and DNA Damage Sensing and Repair Proteins.

Gonzalez-Alvarez M, Severin A, Sayadi M, Keating A Toxicol Sci. 2022; 190(2):173-188.

PMID: 36214631 PMC: 9789752. DOI: 10.1093/toxsci/kfac104.

References

Zepeda-Martinez J, Pribitzer C, Wang J, Bsteh D, Golumbeanu S, Zhao Q . Parallel PRC2/cPRC1 and vPRC1 pathways silence lineage-specific genes and maintain self-renewal in mouse embryonic stem cells. Sci Adv. 2020; 6(14):eaax5692. PMC: 7112768. DOI: 10.1126/sciadv.aax5692. View

Uranishi K, Akagi T, Sun C, Koide H, Yokota T . Dax1 associates with Esrrb and regulates its function in embryonic stem cells. Mol Cell Biol. 2013; 33(10):2056-66. PMC: 3647970. DOI: 10.1128/MCB.01520-12. View

Huang Y, Zhao W, Wang C, Zhu Y, Liu M, Tong H . Combinatorial Control of Recruitment of a Variant PRC1.6 Complex in Embryonic Stem Cells. Cell Rep. 2018; 22(11):3032-3043. DOI: 10.1016/j.celrep.2018.02.072. View

Niwa H, Yamamura K, Miyazaki J . Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene. 1991; 108(2):193-9. DOI: 10.1016/0378-1119(91)90434-d. View

Shum E, Jones S, Shao A, Chousal J, Krause M, Chan W . The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA Decay. Cell. 2016; 165(2):382-95. PMC: 4826573. DOI: 10.1016/j.cell.2016.02.046. View

Katz Y, Wang E, Airoldi E, Burge C . Analysis and design of RNA sequencing experiments for identifying isoform regulation. Nat Methods. 2010; 7(12):1009-15. PMC: 3037023. DOI: 10.1038/nmeth.1528. View

Brogna S, Wen J . Nonsense-mediated mRNA decay (NMD) mechanisms. Nat Struct Mol Biol. 2009; 16(2):107-13. DOI: 10.1038/nsmb.1550. View

Pasini D, Di Croce L . Emerging roles for Polycomb proteins in cancer. Curr Opin Genet Dev. 2016; 36:50-8. DOI: 10.1016/j.gde.2016.03.013. View

Elliott D, Grellscheid S . Alternative RNA splicing regulation in the testis. Reproduction. 2006; 132(6):811-9. DOI: 10.1530/REP-06-0147. View

10.

Uranishi K, Hirasaki M, Kitamura Y, Mizuno Y, Nishimoto M, Suzuki A . Two DNA binding domains of MGA act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells. Stem Cells. 2021; 39(11):1435-1446. DOI: 10.1002/stem.3433. View

11.

Tavares L, Dimitrova E, Oxley D, Webster J, Poot R, Demmers J . RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3. Cell. 2012; 148(4):664-78. PMC: 3281992. DOI: 10.1016/j.cell.2011.12.029. View

12.

Sangrithi M, Royo H, Mahadevaiah S, Ojarikre O, Bhaw L, Sesay A . Non-Canonical and Sexually Dimorphic X Dosage Compensation States in the Mouse and Human Germline. Dev Cell. 2017; 40(3):289-301.e3. PMC: 5300051. DOI: 10.1016/j.devcel.2016.12.023. View

13.

Thorvaldsdottir H, Robinson J, Mesirov J . Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 2012; 14(2):178-92. PMC: 3603213. DOI: 10.1093/bib/bbs017. View

14.

Anderson E, Baltus A, Roepers-Gajadien H, Hassold T, de Rooij D, van Pelt A . Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice. Proc Natl Acad Sci U S A. 2008; 105(39):14976-80. PMC: 2542382. DOI: 10.1073/pnas.0807297105. View

15.

Lin X, Han M, Cheng L, Chen J, Zhang Z, Shen T . Expression dynamics, relationships, and transcriptional regulations of diverse transcripts in mouse spermatogenic cells. RNA Biol. 2016; 13(10):1011-1024. PMC: 5056783. DOI: 10.1080/15476286.2016.1218588. View

16.

Endo T, Mikedis M, Nicholls P, Page D, de Rooij D . Retinoic Acid and Germ Cell Development in the Ovary and Testis. Biomolecules. 2019; 9(12). PMC: 6995559. DOI: 10.3390/biom9120775. View

17.

Scelfo A, Fernandez-Perez D, Tamburri S, Zanotti M, Lavarone E, Soldi M . Functional Landscape of PCGF Proteins Reveals Both RING1A/B-Dependent-and RING1A/B-Independent-Specific Activities. Mol Cell. 2019; 74(5):1037-1052.e7. PMC: 6561742. DOI: 10.1016/j.molcel.2019.04.002. View

18.

Bao J, Tang C, Yuan S, Porse B, Yan W . UPF2, a nonsense-mediated mRNA decay factor, is required for prepubertal Sertoli cell development and male fertility by ensuring fidelity of the transcriptome. Development. 2014; 142(2):352-62. PMC: 4302838. DOI: 10.1242/dev.115642. View

19.

Gao Z, Zhang J, Bonasio R, Strino F, Sawai A, Parisi F . PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. Mol Cell. 2012; 45(3):344-56. PMC: 3293217. DOI: 10.1016/j.molcel.2012.01.002. View

20.

Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P . Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science. 2002; 298(5595):1039-43. DOI: 10.1126/science.1076997. View