bims-hypusi 2026-04-19 papers

Issue of 2026–04–19
two papers selected by
Sebastian J. Hofer, Max Delbrück Center

Elife. 2026 Apr 17. pii: RP107160. [Epub ahead of print]14

Single-mRNA imaging and modeling reveal coupled translation initiation and elongation rates.

Irene Lamberti, Jeffrey A Chao, Cédric Gobet, Felix Naef.

mRNA translation involves multiple regulatory steps, but how translation elongation influences protein output remains unclear. Using SunTag live-cell imaging and mathematical modeling, we quantified translation dynamics in single mRNAs across diverse coding sequences. Our Totally Asymmetric Exclusion Process (TASEP)-based Hidden Markov Model revealed a strong coordination between initiation and elongation rates, resulting in consistently low ribosome density (≤12% occupancy) across all reporters. This coupling persisted under pharmacological inhibition of the elongation factor eIF5A, where proportional decreases in both initiation and elongation rates maintained homeostatic ribosome density. In contrast, eIF5A knockout cells exhibited a significant decrease in ribosome density, suggesting altered coordination. Together, these results highlight a dynamical coupling of initiation and elongation rates at the single-mRNA level, preventing ribosome crowding and maintaining translational homeostasis in mammalian cells.

Keywords: SunTag; TASEP; computational biology; eIF5A; human; single-molecule imaging; systems biology; translation elongation

DOI: https://doi.org/10.7554/eLife.107160

Zool Res. 2026 Mar 18. pii: 2095-8137(2026)02-0503-16. [Epub ahead of print]47(2): 503-518

Male germ cell-specific deletion of Eif5 causes the apoptosis of mouse progenitor spermatogonia by excessive endoplasmic reticulum stress and defective DNA repair.

Hongwei Wei, Yating Huang, Weiyong Wang, Shuang Liu, Huiyu Liu, Hanyu Chu, Yan-Li Sun, Yan Du, Wenqian Li, Luchun Zhang, Yashuang Weng, Wenbo Zhang, Meijia Zhang, Zhijuan Wang.

Idiopathic non-obstructive azoospermia (iNOA) is associated with reduced expression of multiple eukaryotic translation initiation factors ( EIFs) in spermatogonia, including eukaryotic translation initiation factor 5 ( EIF5). The present study revealed that eIF5 mRNA and protein levels were markedly higher in male mouse ( Mus musculus) germ cells than in Leydig or Sertoli cells. Thus, to define the role of eIF5 in spermatogenesis, Eif5 conditional knockout (cKO) mice were generated by crossing Eif5 fl/fl mice with Stimulated by retinoic acid 8 ( Stra8)-Cre mice. Loss of Eif5 in male germ cells reduced both SRY-box transcription factor 3 (SOX3) + progenitor spermatogonia and Kit proto-oncogene receptor tyrosine kinase (KIT) + differentiating spermatogonia, leading to severe meiotic failure and complete male infertility. Mechanistically, Eif5 deficiency impaired translation of genes involved in ubiquitination, autophagy, and DNA repair, which, in turn, triggered excessive endoplasmic reticulum (ER) stress and compromised DNA repair in SOX3 + progenitor spermatogonia. These defects promoted DNA damage and subsequent apoptosis, resulting in progressive germ cell depletion and sterility. Collectively, these findings highlight the essential role of eIF5 in spermatogenesis and offer a potential therapeutic strategy for iNOA associated with reduced expression of EIF5 and other translation initiation factors.

Keywords: DNA repair; Endoplasmic reticulum stress; Male infertility; eIF5

DOI: https://doi.org/10.24272/j.issn.2095-8137.2025.220