Accumulating evidences suggest that the composition and functional roles of ribosomes are heterogeneous in cells, partly due to the temporal-spatial expression of paralogous ribosomal proteins (RPs), of which functional relationships remain largely unexplored. In mouse, the X chromosome-linked RPL39 and its male germline specific paralog RPL39L are thought to express mutually exclusively due to the meiotic sex chromosome inactivation, hinders the understanding of their functional relationships. In the present study, we investigated the expression and functional relations of Rpl39 and Rpl39l in a proliferative mouse cell line, in which both genes are expressed simultaneously, with the expression level of Rpl39 higher than that of Rpl39l. Disruption of Rpl39 via CRISPR/Cas9 method caused decreased cell proliferation, nascent protein synthesis and altered mitochondrial functions, whereas double mutations of Rpl39 and Rpl39l augmented these phenotypes, suggesting that both RPs contribute to the cellular physiology. Consistently, overexpression of Rpl39, Rpl39l or an alanine mutant of RPL39, rescued cell proliferation similarly in Rpl39^-/-::Rpl39l^-/- dual gene null cells. Deletion of Rpl39l induced compensatory expression of Rpl39, rendering the deleterious effects of Rpl39l mutation. Supporting this, Rpl39l mutation was more detrimental to cells under a low serum condition, under which the compensatory expression of Rpl39 was inhibited. Moreover, the low serum condition induced expression of both genes, suggesting that they possess stress responsive roles. Taken together, these data indicate that both RPL39 and RPL39L influence cell proliferation via protein synthesis and mitochondrial functions, suggesting a link between protein translation and cellular metabolism through these ribosomal protein paralogs.

越来越多的证据表明，细胞中核糖体的组成和功能作用是异质的，部分原因是旁系同源核糖体蛋白（RP）的时空表达，其功能关系在很大程度上仍未被探索。在小鼠中，由于减数分裂性染色体失活，X染色体连接的RPL39及其雄性种系特异性旁系同源物RPL39L被认为是相互排斥表达的，这阻碍了对它们功能关系的理解。在本研究中，我们研究了增殖小鼠细胞系中Rpl39和Rpl39l的表达和功能关系，其中两个基因同时表达，且Rpl39的表达水平高于Rpl39l 。通过 CRISPR/Cas9 方法破坏Rpl39会导致细胞增殖减少、新生蛋白质合成和线粒体功能改变，而Rpl39和Rpl39l的双突变增强了这些表型，表明两种 RP 都有助于细胞生理学。一致地， Rpl39 、 Rpl39l或RPL39的丙氨酸突变体的过表达在Rpl39 ^-/- ::Rpl39l ^-/-双基因无效细胞中类似地挽救了细胞增殖。 Rpl39l的缺失诱导Rpl39的补偿性表达，呈现Rpl39l突变的有害影响。支持这一点的是， Rpl39l突变在低血清条件下对细胞更加有害，在低血清条件下， Rpl39的补偿性表达受到抑制。 此外，低血清条件诱导这两种基因的表达，表明它们具有应激反应作用。总而言之，这些数据表明 RPL39 和 RPL39L 通过蛋白质合成和线粒体功能影响细胞增殖，表明蛋白质翻译和细胞代谢之间通过这些核糖体蛋白质旁系同源物存在联系。