@article{8b65c2695f184555ab16e554708e3952,
title = "MRNIP interacts with sex body chromatin to support meiotic progression, spermatogenesis, and male fertility in mice",
abstract = "Meiosis has a principal role in sexual reproduction to generate haploid gametes in both sexes. During meiosis, the cell nucleus hosts a dynamic environment where some genes are transcriptionally activated, and some are inactivated at the same time. This becomes possible through subnuclear compartmentalization. The sex body, sequestering X and Y chromosomes during male meiosis and creating an environment for the meiotic sex chromosome inactivation (MSCI) is one of the best known and studied subnuclear compartments. Herein, we show that MRNIP forms droplet-like accumulations that fuse together to create a distinct subnuclear compartment that partially overlaps with the sex body chromatin during diplotene. We demonstrate that Mrnip−/− spermatocytes have impaired DNA double-strand break (DSB) repair, they display reduced sex body formation and defective MSCI. We show that Mrnip−/− undergoes critical meiocyte loss at the diplotene stage. Furthermore, we determine that DNA DSBs (induced by SPO11) and synapsis initiation (facilitated by SYCP1) precede Mrnip expression in testes. Altogether, our findings indicate that in addition to an emerging role in DNA DSB repair, MRNIP has an essential function in spermatogenesis during meiosis I by forming drop-like accumulations interacting with the sex body.",
keywords = "XY body, diplotene, liquid–liquid phase separation, male infertility, pachytene, subnuclear",
author = "Samina Kazi and Casta{\~n}eda, {Julio M.} and Audrey Savolainen and Yiding Xu and Ning Liu and Huanyu Qiao and Ramiro Ramirez-Solis and Kaori Nozawa and Zhifeng Yu and Matzuk, {Martin M.} and Renata Prunskaite-Hyyryl{\"a}inen",
note = "Funding Information: We thank Fenna van Rijt, Julio Agno, Johanna Kekolahti-Liias, Paula Haipus, Philomena Schmid, C{\'e}lia Tebbakh, and Teemu Lappalainen for technical assistance. We thank Prof. Lari Lehti{\"o} for valuable feedback on this manuscript. We gratefully acknowledge the services of the Biocenter Oulu Transgenic core facility, a member of Biocenter Finland and Infrafrontier-EMMA. This work was supported by grants from the Academy of Finland 285151 and Profi6 336449 and the Sigrid Jus{\'e}lius Foundation to R. P.-H.; Health and Bioscience doctoral program of the University of Oulu to S.K. and A.S.; the Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japan Society for the Promotion of Science (JSPS) KAKENHI grants JP18K14715 and JP20K15804 to JMC; National Institute of Health R00 HD082375 and R01 GM135549 to H.Q.; a P30 Cancer Center Support Grant (NCI-CA125123, HTAP), the Eunice Kennedy Shriver National Institute of Child Health and Human Development R01HD088412 and P01HD087157 to M.M.M., and the Bill & Melinda Gates Foundation INV-001902 to M.M.M. Funding Information: We thank Fenna van Rijt, Julio Agno, Johanna Kekolahti‐Liias, Paula Haipus, Philomena Schmid, C{\'e}lia Tebbakh, and Teemu Lappalainen for technical assistance. We thank Prof. Lari Lehti{\"o} for valuable feedback on this manuscript. We gratefully acknowledge the services of the Biocenter Oulu Transgenic core facility, a member of Biocenter Finland and Infrafrontier‐EMMA. This work was supported by grants from the Academy of Finland 285151 and Profi6 336449 and the Sigrid Jus{\'e}lius Foundation to R. P.‐H.; Health and Bioscience doctoral program of the University of Oulu to S.K. and A.S.; the Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japan Society for the Promotion of Science (JSPS) KAKENHI grants JP18K14715 and JP20K15804 to JMC; National Institute of Health R00 HD082375 and R01 GM135549 to H.Q.; a P30 Cancer Center Support Grant (NCI‐CA125123, HTAP), the Eunice Kennedy Shriver National Institute of Child Health and Human Development R01HD088412 and P01HD087157 to M.M.M., and the Bill & Melinda Gates Foundation INV‐001902 to M.M.M. Publisher Copyright: {\textcopyright} 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.",
year = "2022",
month = sep,
doi = "10.1096/fj.202101168RR",
language = "English (US)",
volume = "36",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "9",
}