The nuclear exosome co-factor MTR4 shapes the transcriptome for meiotic initiation

Li Zhang, Jianshu Wang, Zhidong Tang, Zhen Lin, Ruibao Su, Naijing Hu, Yao Tang, Gaoxiang Ge, Jing Fan, Ming-Han Tong, Yuanchao Xue (), Yu Zhou () and Hong Cheng ()
Additional contact information
Li Zhang: University of Chinese Academy of Sciences
Jianshu Wang: University of Chinese Academy of Sciences
Zhidong Tang: Wuhan University
Zhen Lin: University of Chinese Academy of Sciences
Ruibao Su: Chinese Academy of Sciences
Naijing Hu: Chinese Academy of Sciences
Yao Tang: Wuhan University
Gaoxiang Ge: University of Chinese Academy of Sciences
Jing Fan: University of Chinese Academy of Sciences
Ming-Han Tong: University of Chinese Academy of Sciences
Yuanchao Xue: Chinese Academy of Sciences
Yu Zhou: Wuhan University
Hong Cheng: University of Chinese Academy of Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Nuclear RNA decay has emerged as a mechanism for post-transcriptional gene regulation in cultured cells. However, whether this process occurs in animals and holds biological relevance remains largely unexplored. Here, we demonstrate that MTR4, the central cofactor of the nuclear RNA exosome, is essential for embryogenesis and spermatogenesis. Embryonic development of Mtr4 knockout mice arrests at 6.5 day. Germ cell-specific knockout of Mtr4 results in male infertility with a specific and severe defect in meiotic initiation. During the pre-meiotic stage, MTR4/exosome represses meiotic genes, which are typically shorter in size and possess fewer introns, through RNA degradation. Concurrently, it ensures the expression of mitotic genes generally exhibiting the opposite features. Consistent with these regulation rules, mature replication-dependent histone mRNAs and polyadenylated retrotransposon RNAs were identified as MTR4/exosome targets in germ cells. In addition, MTR4 regulates alternative splicing of many meiotic genes. Together, our work underscores the importance of nuclear RNA degradation in regulating germline transcriptome, ensuring the appropriate gene expression program for the transition from mitosis to meiosis during spermatogenesis.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57898-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57898-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57898-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().