University of Oulu

Kazi, S., Castañeda, J. M., Savolainen, A., Xu, Y., Liu, N., Qiao, H., Ramirez‐Solis, R., Nozawa, K., Yu, Z., Matzuk, M. M., & Prunskaite‐Hyyryläinen, R. (2022). mrnip interacts with sex body chromatin to support meiotic progression, spermatogenesis, and male fertility in mice. The FASEB Journal, 36(9).

MRNIP interacts with sex body chromatin to support meiotic progression, spermatogenesis, and male fertility in mice

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Author: Kazi, Samina1; Castañeda, Julio M.2; Savolainen, Audrey1;
Organizations: 1Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
2Research Institute for Microbial Diseases, Osaka University, Suita, Japan
3Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
4University of Texas Health Science Center, San Antonio, Texas, USA
5Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA
6Center for Drug Discovery, Baylor College of Medicine, Houston, Texas, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 9.7 MB)
Persistent link:
Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2022-11-16


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.

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Series: The FASEB journal
ISSN: 0892-6638
ISSN-E: 1530-6860
ISSN-L: 0892-6638
Volume: 36
Issue: 9
Article number: e22479
DOI: 10.1096/fj.202101168rr
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was supported by grants from the Academy of Finland 285151 and Profi6 336449 and the Sigrid Jusélius 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.
Academy of Finland Grant Number: 285151
Detailed Information: 285151 (Academy of Finland Funding decision)
Dataset Reference: The data that support the findings of this study are available in the methods and/or supplementary material of this article.
Copyright information: © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.