bims-hypusi 2025-08-03 papers

Issue of 2025–08–03
two papers selected by
Sebastian J. Hofer, Max Delbrück Center

Poult Sci. 2025 Jul 26. pii: S0032-5791(25)00843-0. [Epub ahead of print]104(10): 105602

Spermidine enhances steroidogenesis by elevating eIF5Ahyp level in hierarchical follicular granulosa cells of the goose.

Dongmei Jiang, Chengweng Ji, Qian Sun, Yuxin Qi, Shuo Li, Xiaoguang An, Weikang Ling, Xin Wang, Chunyang Niu, Bo Kang.

Imbalanced steroid hormone levels in female poultry can impair follicular development, thereby adversely affecting reproductive performance. Spermidine is reported to be involved in regulation of female reproduction and can provide aminobutyl as the only substrate required for the activation of eukaryotic translation initiation factor 5A (eIF5Ahyp). In this study, goose granulosa cells were treated with spermidine and interference/overexpression eIF5A with the aim of investigating the effects and mechanisms of spermidine on steroidogenesis. Estradiol (E2) and progesterone (P4) levels increased with spermidine concentration, peaking at 160 μmol/L (P < 0.01). Compared with control, eIF5A overexpression significantly increased E2 levels (P < 0.05), but had no effect on P4. Moreover, compared with the eIF5A overexpression, 160 μmol/L spermidine combined with eIF5A overexpression treatment further increased E2 level (P < 0.05). Mechanistically, we found that both spermidine and eIF5A overexpression treatments significantly increased eIF5Ahyp as well as StAR protein expression (P < 0.05). These results suggest that spermidine can enhance steroidogenic capacity of goose granulosa cells, and this effect is mainly realized by mediating eIF5Ahyp. Notably, protein functional annotation revealed that differentially expressed proteins were significantly enriched in steroid biosynthesis and metabolism pathways. HMOX1, COQ9, and SERPINE2 were preliminarily identified as key proteins for spermidine-eIF5Ahyp axis-regulated steroidogenesis in goose granulosa cells.

Keywords: eIF5A hypusination; goose granulosa cells; spermidine; steroidogenesis

DOI: https://doi.org/10.1016/j.psj.2025.105602

Nat Struct Mol Biol. 2025 Jul 28.

eIF1 and eIF5 dynamically control translation start site fidelity.

Rosslyn Grosely, Carlos Alvarado, Ivaylo P Ivanov, Oliver B Nicholson, Joseph D Puglisi, Thomas E Dever, Christopher P Lapointe.

Human translation initiation requires accurate recognition of translation start sites. While AUG codons are canonical start sites, non-AUG codons are also used, typically with lower efficiency. The initiator tRNA and initiation factors eIF1 and eIF5 control recognition. How they distinguish different start sites yet allow flexible recognition remains unclear. Here we used real-time single-molecule assays and an in vitro reconstituted human system to reveal how eIF1 and eIF5 direct start site selection. eIF1 binds initiation complexes in two modes: stable binding during scanning, followed by transient, concentration-dependent rebinding after start site recognition. Termination of eIF1 rebinding requires transient and concentration-dependent binding by eIF5, which allows the formation of translation competent ribosomes. Non-AUG start sites differentially stabilize eIF1 and destabilize eIF5 binding, blocking initiation at multiple points. We confirmed these opposing effects in human cells. Collectively, our findings uncover that eIF1 and eIF5 directly compete to bind initiation complexes and illuminate how their dynamic interplay tunes the fidelity of start site recognition, which has broad connections to health and disease.

DOI: https://doi.org/10.1038/s41594-025-01629-y