A Dual Program for Translation Regulation in Cellular Proliferation and Differentiation
A Dual Program for Translation Regulation in Cellular Proliferation and Differentiation
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DOI：
10.1016/j.cell.2014.08.011
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发表时间：
2014-09-11
期刊：
影响因子：
64.5
通讯作者：
Pilpel, Yitzhak
中科院分区：
文献类型：
--
作者：
Gingold, Hila;Tehler, Disa;Pilpel, Yitzhak
后生动物细胞的二分选择是增殖和分化。通过测量各种细胞类型中的tRNA库，我们发现了两个不同的子集，一个在增殖细胞中被诱导，另一个则被抑制，另一个则具有相反的特征。相应地，我们发现，基因服务的细胞自主功能和基因参与多细胞服从不同的密码子使用。增殖诱导和分化诱导的tRNA通常携带反密码子，这些反密码子分别对应于细胞自主基因和多细胞基因中富集的密码子。由于细胞自主基因的mRNA在增殖和癌症中被诱导，特别是伴随着其密码子富集的tRNA的诱导，表明转录和翻译之间的协调。组蛋白修饰确实在细胞自主基因及其相应的tRNA附近发生类似的变化，并且在多细胞基因及其tRNA中发生类似的变化，这表明存在协调tRNA供应和需求的转录程序。因此，我们描述了两个不同的翻译程序，在增殖和分化过程中运作的存在。
A dichotomous choice for metazoan cells is between proliferation and differentiation. Measuring tRNA pools in various cell types, we found two distinct subsets, one that is induced in proliferating cells, and repressed otherwise, and another with the opposite signature. Correspondingly, we found that genes serving cell-autonomous functions and genes involved in multicellularity obey distinct codon usage. Proliferation-induced and differentiation-induced tRNAs often carry anticodons that correspond to the codons enriched among the cell-autonomous and the multicellularity genes, respectively. Because mRNAs of cell-autonomous genes are induced in proliferation and cancer in particular, the concomitant induction of their codon-enriched tRNAs suggests coordination between transcription and translation. Histone modifications indeed change similarly in the vicinity of cell-autonomous genes and their corresponding tRNAs, and in multicellularity genes and their tRNAs, suggesting the existence of transcriptional programs coordinating tRNA supply and demand. Hence, we describe the existence of two distinct translation programs that operate during proliferation and differentiation.