传统上，人们认为细胞内所有的核糖体其生化组成都是固定的，功能也是单一的。但是随着在多种物种中陆续发现了核糖体异质性，这种观点正被逐渐改变。核糖体异质性学说认为，核糖体在组成和功能上都是可变的。然而，现在还不清楚这些异质核糖体的生化基础及其功能差异的分子机制。.我们在裂殖酵母中已经发现核糖体小亚基蛋白S8旁系同源蛋白Rps801p和Rps802p造成大亚基蛋白L42蛋白含量的差异，提出基于S8/L42核糖体异质性的工作模型。本项目将以此为研究对象，在裂殖酵母核糖体中直接验证这一工作模型，并且阐明S8/L42异质核糖体的生物学功能，最终探索异质核糖体差异性翻译的靶基因。.本项目的成功将第一次从生化水平上阐明核糖体异质性的组成并且为核糖体异质性提供生化、遗传等多学科综合的实验证据支持，为核糖体病变的解决和药物靶点的选择提供指导。

It is commonly thought that all ribosome particles in cells have the same biochemical composition, and carry out one activity of protein translation. However, such paradigm is challenged by the alternative hypothesis of ribosome heterogeneity, which postulates that ribosomes may have variable compositions and may differentially translate specific mRNAs. The biochemical nature of ribosome heterogeneity and the mechanisms underlying the differential functions of heterogeneous ribosomes remain largely unknown..Our preliminary investigation in the fission yeast have indicated that ribosome composition may vary depending on which of the rps8 paralogs (Rps801p or Rps802p) is incorporated into the 80S ribosome particle, which in turn, may influence whether Rpl42p is incorporated or not. .Here, we propose to test directly the existence of ribosome heterogeneity in fission yeast mediated by Rps8/Rpl42. We will further explore its functional significance by testing the possible anti-stress growth advantages conveyed by ribosome heterogeneity. Lastly, we seek to identify the target mRNAs that are differentially translated by heterogenous ribosomes..The success of these proposed work will for the first time establish the biochemical basis for ribosome heterogeneity and provide a comprehensive set of supporting evidence integrating results deriving from biochemical, genetic and high-throughput investigations.