Protein degradation shapes developmental tempo in mouse and human neural progenitors
biorxiv(2024)
摘要
The speed of embryonic development varies considerably between mammalian species, yet the underlying molecular mechanisms remain poorly understood. To investigate the basis for species-specific developmental tempo we performed a comprehensive comparative analysis of protein dynamics in mouse and human neural progenitors (NPs). Through a combination of targeted protein labelling, quantitative mass spectrometry, and functional genomics, we demonstrate that protein degradation is a key driver of tempo differences between mouse and human NPs. We observe a systematic 1.5-fold increase in protein half-lives in human NPs compared to mouse, independent of cellular compartment or protein function. This difference persists in post-mitotic neurons, indicating active degradation as the primary mechanism. Proteasomal activity is also ~1.5-fold higher in mouse NPs, consistent with upregulation of proteasome-associated proteins. Importantly, increasing the rate of proteolytic degradation of a key transcriptional repressor in neural progenitors accelerates the expression of its target gene. Despite differences in degradation rates, protein synthesis rates are similar between species, resulting in higher protein content in human NPs. Our findings highlight the central role of protein degradation in controlling developmental tempo and provide insight into the molecular basis of evolutionary changes in developmental timing across species.
### Competing Interest Statement
The authors have declared no competing interest.
更多查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要