EIF5A Couples Translational Control With Transcriptional Reprogramming Through Chromocenter Reorganization During Spermiogenesis

TL;DR

eIF5A is crucial for male fertility by organizing chromatin and regulating protein translation during sperm development.

Contribution

eIF5A's dual role in translational and transcriptional regulation during spermiogenesis is newly characterized.

Findings

eIF5A deficiency disrupts chromocenter integrity and causes infertility in male mice.

eIF5A regulates chromatin accessibility and transcription of genes involved in acrosome and manchette formation.

Loss of eIF5A leads to translational dysregulation of chromatin-organizing proteins.

Abstract

Eukaryotic translation initiation factor 5A (eIF5A) facilitates protein synthesis and impacts diverse biological processes, yet its role in transcriptional regulation is poorly understood. Here eIF5A highly expressed in diverse spermatogenic cell types are found. Conditional knockout of Eif5a (SKO) causes complete infertility in male mice due to round spermatid arrest. Interestingly, eIF5A deletion severely compromises chromocenter integrity in round spermatids. Proteomic profiling reveals widespread dysregulation in eIF5A‐deficient round spermatids, downregulated proteins are enriched for chromatin‐associated functions, likely contributing to chromocenter dysfunction. Notably, ATAC‐seq (Assay for Transposase‐Accessible Chromatin with high‐throughput sequencing) analysis shows increased chromatin accessibility upon eIF5A depletion, accompanied by transcriptional dysregulation of genes critical for acrosome and manchette formation. This data underscore that eIF5A not only regulates the translation of chromatin‐organizing proteins required for chromocenter stability but also influences transcriptional regulation by modulating chromatin landscape. These findings illuminate a previously uncharacterized and germ cell‐specific pathway coupling translational control and transcriptional regulation via chromatin reorganization.

The translation factor Eukaryotic translation initiation factor 5A (eIF5A) is essential for male fertility in mice. It supports the translation of proteins crucial for heterochromatin organization and acrosome formation. eIF5A deficiency disrupts chromocenter integrity, increases chromatin accessibility, and causes transcriptional dysregulation, leading to defects in acrosome and manchette formation that arrest spermatid development.

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