eEF1G Orchestrates Translation to Ensure Meiotic Progression in Transcriptionally Quiescent Spermatocytes
Source abstract
Abstract
ABSTRACT During meiotic prophase I, mammalian spermatocytes must synthesize large amounts of recombination and synapsis proteins despite global transcriptional suppression at the leptotene/zygotene (L/Z) stages. Here, we identify eukaryotic translation elongation factor 1 gamma (eEF1G), highly expressed in spermatogenic cells, as a factor essential for sustaining translation during this transcriptionally quiescent period. Germ cell–specific Eef1g knockout causes complete male infertility due to zygotene arrest, characterized by defects in recombination intermediate stabilization and synapsis. Mechanistically, eEF1G associates with ribosomal proteins, and ribosome profiling reveals increased ribosome occupancy on specific meiotic transcripts in Eef1g ‐deficient spermatocytes. Quantitative proteomics further reveals selective depletion of synapsis‐related (e.g., SYCP1, SYCE1) and recombination‐related proteins (e.g., MSH4, TEX11). Together, these findings demonstrate that eEF1G is required to maintain efficient protein production during the transcriptionally quiescent leptotene/zygotene stages, thereby supporting proper meiotic progression in mammalian spermatocytes.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: DNA Repair Mechanisms · Bacterial Genetics and Biotechnology · Mitochondrial Function and Pathology
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health Shandong University Shandong P. R. China
National Research Center for Assisted Reproductive Technology and Reproductive Genetics Shandong University Jinan Shandong P. R. China
Key Laboratory of Reproductive Endocrinology, Ministry of Education Shandong University Jinan Shandong P. R. China
Shandong Technology Innovation Center for Reproductive Health Jinan Shandong P. R. China
Shandong Provincial Clinical Research Center for Reproductive Health Jinan Shandong P. R. China
School of Basic Medical Sciences Shandong University Jinan Shandong P. R. China
Jinan Maternal and Child Health Care Hospital Jinan Shandong P. R. China
Center for Reproduction and Genetics, Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui P. R. China
Funding
National Natural Science Foundation of China · Natural Science Foundation of Shandong Province · National Key Research and Development Program of China · Fundamental Research Funds for the Central Universities
References (95)
Show source-provided references
1. 10.1038/s41586‐024‐08574‐810.1038/s41586‐024‐08574‐8 ↗
2. 10.1126/science.aad530910.1126/science.aad5309 ↗
3. 10.1038/s41586‐024‐08551‐110.1038/s41586‐024‐08551‐1 ↗
4. 10.1126/science.aad519610.1126/science.aad5196 ↗
5. 10.1146/annurev‐genom‐110122‐09023910.1146/annurev‐genom‐110122‐090239 ↗
6. C14ORF39/SIX6OS1 is a Constituent of the Synaptonemal Complex and is Essential for Mouse Fertility10.1038/ncomms13298 ↗
7. 10.1038/s41576‐023‐00669‐810.1038/s41576‐023‐00669‐8 ↗
8. 10.1101/cshperspect.a01661810.1101/cshperspect.a016618 ↗
9. 10.1038/s41594‐022‐00909‐110.1038/s41594‐022‐00909‐1 ↗
10. Mouse Sycp1 Functions in Synaptonemal Complex Assembly, Meiotic Recombination, and XY Body Formation10.1101/gad.329705 ↗
11. 10.1016/j.ajhg.2021.01.01010.1016/j.ajhg.2021.01.010 ↗
12. Mutation of the Mouse Syce1 Gene Disrupts Synapsis and Suggests a Link between Synaptonemal Complex Structural Components and DNA Repair10.1371/journal.pgen.1000393 ↗
13. Meiotic Chromosome Synapsis Depends on Multivalent SYCE1‐SIX6OS1 Interactions That Are Disrupted in Cases of human Infertility10.1126/sciadv.abb1660 ↗
14. 10.1093/nar/gkaf14610.1093/nar/gkaf146 ↗
15. 10.1038/s41467‐019‐09182‐110.1038/s41467‐019‐09182‐1 ↗
16. 10.1038/s41422‐018‐0128‐110.1038/s41422‐018‐0128‐1 ↗
17. 10.1101/cshperspect.a03264910.1101/cshperspect.a032649 ↗
18. 10.1038/s41392‐024‐01749‐910.1038/s41392‐024‐01749‐9 ↗
19. 10.1038/s41580‐023‐00624‐910.1038/s41580‐023‐00624‐9 ↗
20. 10.1186/s11658‐024‐00674‐710.1186/s11658‐024‐00674‐7 ↗
21. 10.1080/15476286.2025.250472710.1080/15476286.2025.2504727 ↗
22. 10.1074/jbc.R110.11379510.1074/jbc.R110.113795 ↗
23. 10.1002/humu.2367710.1002/humu.23677 ↗
24. 10.3389/fmicb.2018.0144610.3389/fmicb.2018.01446 ↗
25. Translation Termination and Ribosome Recycling in Eukaryotes10.1101/cshperspect.a032656 ↗
26. 10.1042/BST2022058410.1042/BST20220584 ↗
27. 10.1016/j.celrep.2025.11563910.1016/j.celrep.2025.115639 ↗
28. 10.3389/fmolb.2021.81639810.3389/fmolb.2021.816398 ↗
29. 10.1242/dev.19957310.1242/dev.199573 ↗
30. 10.1002/wrna.111810.1002/wrna.1118 ↗
31. 10.1126/science.abj664710.1126/science.abj6647 ↗
32. EEF1B2 Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cell Lines Through TAF4B10.1016/j.heliyon.2024.e36467 ↗
33. Heterozygous Mutation of eEF1A1b Resulted in Spermatogenesis Arrest and Infertility in Male Tilapia10.1038/srep43733 ↗
34. 10.1016/j.lfs.2019.11697710.1016/j.lfs.2019.116977 ↗
35. 10.1038/s41592‐022‐01526‐y10.1038/s41592‐022‐01526‐y ↗
36. 10.1074/mcp.RA120.00208110.1074/mcp.RA120.002081 ↗
37. 10.1038/cr.2017.11710.1038/cr.2017.117 ↗
38. 10.1016/j.cub.2017.04.01710.1016/j.cub.2017.04.017 ↗
39. 10.1016/j.molcel.2019.03.02210.1016/j.molcel.2019.03.022 ↗
40. 10.1016/j.celrep.2022.11054010.1016/j.celrep.2022.110540 ↗
41. The BRCA2‐MEILB2‐BRME1 Complex Governs Meiotic Recombination and Impairs the Mitotic BRCA2‐RAD51 Function in Cancer Cells10.1038/s41467-020-15954-x ↗
42. 10.1038/s41594‐021‐00636‐z10.1038/s41594‐021‐00636‐z ↗
43. Mouse HORMAD1 and HORMAD2, Two Conserved Meiotic Chromosomal Proteins, Are Depleted from Synapsed Chromosome Axes with the Help of TRIP13 AAA‐ATPase10.1371/journal.pgen.1000702 ↗
44. 10.1038/ng0796‐33610.1038/ng0796‐336 ↗
45. Mutation in Mouse Hei10, an E3 Ubiquitin Ligase, Disrupts Meiotic Crossing Over10.1371/journal.pgen.0030139 ↗
46. 10.1038/ng.285810.1038/ng.2858 ↗
47. 10.1038/s41467‐020‐16885‐310.1038/s41467‐020‐16885‐3 ↗
48. 10.1126/science.aaf640710.1126/science.aaf6407 ↗
49. 10.1038/s41421‐023‐00577‐510.1038/s41421‐023‐00577‐5 ↗
50. 10.1038/s42003‐018‐0154‐z10.1038/s42003‐018‐0154‐z ↗
51. 10.1016/j.molcel.2020.06.01510.1016/j.molcel.2020.06.015 ↗
52. 10.1016/j.molcel.2013.02.02010.1016/j.molcel.2013.02.020 ↗
53. 10.1002/0471142956.cy0744s7210.1002/0471142956.cy0744s72 ↗
54. 10.1083/jcb.20061002710.1083/jcb.200610027 ↗
55. 10.1242/jcs.03323310.1242/jcs.033233 ↗
56. 10.1016/j.celrep.2019.05.09610.1016/j.celrep.2019.05.096 ↗
57. A Meiosis‐Specific BRCA2 Binding Protein Recruits Recombinases to DNA Double‐Strand Breaks to Ensure Homologous Recombination10.1038/s41467-019-08676-2 ↗
58. 10.1095/biolreprod.111.09575210.1095/biolreprod.111.095752 ↗
59. 10.1093/humrep/deab18510.1093/humrep/deab185 ↗
60. MEIOB Targets Single‐Strand DNA and Is Necessary for Meiotic Recombination10.1371/journal.pgen.1003784 ↗
61. 10.1093/nar/gkaa101610.1093/nar/gkaa1016 ↗
62. 10.1038/ncomms378810.1038/ncomms3788 ↗
63. 10.1126/sciadv.aax110110.1126/sciadv.aax1101 ↗
64. ZCWPW1 is Recruited to Recombination Hotspots by PRDM9 and is Essential for Meiotic Double Strand Break Repair10.7554/eLife.53392 ↗
65. 10.1038/s41467‐024‐53641‐310.1038/s41467‐024‐53641‐3 ↗
66. 10.1093/nar/gkt123410.1093/nar/gkt1234 ↗
67. 10.1242/jcs.21441110.1242/jcs.214411 ↗
68. 10.1038/s41467‐018‐07798‐310.1038/s41467‐018‐07798‐3 ↗
69. 10.1038/s41467‐018‐04851‐z10.1038/s41467‐018‐04851‐z ↗
70. 10.1038/s41467‐018‐04850‐010.1038/s41467‐018‐04850‐0 ↗
71. Meiotic Cohesin SMC1β Provides Prophase I Centromeric Cohesion and Is Required for Multiple Synapsis‐Associated Functions10.1371/journal.pgen.1003985 ↗
72. Distinct Roles of Meiosis‐Specific Cohesin Complexes in Mammalian Spermatogenesis10.1371/journal.pgen.1006389 ↗
73. 10.1038/emboj.2011.22210.1038/emboj.2011.222 ↗
74. 10.1073/pnas.161846511410.1073/pnas.1618465114 ↗
75. 10.1038/s41467‐021‐23550‐w10.1038/s41467‐021‐23550‐w ↗
76. 10.1016/j.cell.2015.10.03010.1016/j.cell.2015.10.030 ↗
77. 10.1038/s41418‐017‐0037‐810.1038/s41418‐017‐0037‐8 ↗
78. 10.1038/ncb289610.1038/ncb2896 ↗
79. 10.1093/biolre/ioaa00210.1093/biolre/ioaa002 ↗
80. 10.1016/j.molcel.2017.03.00310.1016/j.molcel.2017.03.003 ↗
81. 10.1186/s12859‐020‐03670‐810.1186/s12859‐020‐03670‐8 ↗
82. 10.1038/ncomms1032410.1038/ncomms10324 ↗
83. 10.24272/j.issn.2095‐8137.2025.22010.24272/j.issn.2095‐8137.2025.220 ↗
84. 10.1002/advs.20251742310.1002/advs.202517423 ↗
85. 10.1038/s41556‐024‐01442‐710.1038/s41556‐024‐01442‐7 ↗
86. 10.1016/j.cell.2018.01.03510.1016/j.cell.2018.01.035 ↗
87. 10.1016/j.molcel.2012.12.00110.1016/j.molcel.2012.12.001 ↗
88. 10.3390/ijms2206326410.3390/ijms22063264 ↗
89. 10.1038/s41585‐023‐00837‐910.1038/s41585‐023‐00837‐9 ↗
90. 10.1002/cyto.a.2246310.1002/cyto.a.22463 ↗
91. 10.1016/j.cell.2019.11.02210.1016/j.cell.2019.11.022 ↗
92. 10.21769/BioProtoc.468610.21769/BioProtoc.4686 ↗
93. 10.1038/s41587‐019‐0201‐410.1038/s41587‐019‐0201‐4 ↗
94. 10.1093/bioinformatics/btt65610.1093/bioinformatics/btt656 ↗
95. 10.1038/s41594‐023‐01119‐z10.1038/s41594‐023‐01119‐z ↗