Gene expression is extensively and dynamically modulated at the level of translation. How cancer cells prioritize the translation of certain mRNAs over others from a pool of competing mRNAs remains an open question. Here, we analyze translation in cell line models of breast cancer and normal mammary tissue by ribosome profiling. We identify key recurrent themes of oncogenic translation: higher ribosome occupancy, greater variance of translational efficiencies, and preferential translation of transcriptional regulators and signaling proteins in malignant cells as compared with their nonmalignant counterpart. We survey for candidate RNA interacting proteins that could associate with the 5′untranslated regions of the transcripts preferentially translated in breast tumour cells. We identify SRSF1, a prototypic splicing factor, to have a pervasive direct and indirect impact on translation. In a representative estrogen receptor–positive and estrogen receptor–negative cell line, we find that protein synthesis relies heavily on SRSF1. SRSF1 is predominantly intranuclear. Under certain conditions, SRSF1 translocates from the nucleus to the cytoplasm where it associates with MYC and CDK1 mRNAs and upregulates their internal ribosome entry site–mediated translation. Our results point to a synergy between splicing and translation and unveil how certain RNA-binding proteins modulate the translational landscape in breast cancer.

基因表达在翻译水平上被广泛且动态地调节。癌细胞如何从竞争性mRNA的集合中优先于某些mRNA的翻译仍然是一个悬而未决的问题。在这里，我们通过核糖体分析来分析乳腺癌和正常乳腺组织的细胞系模型中的翻译。我们确定了致癌翻译的关键复发主题：与非恶性肿瘤相比，更高的核糖体占有率，更大的翻译效率差异以及转录调节因子和信号蛋白的优先翻译。我们调查了可能与优先在乳腺肿瘤细胞中翻译的转录本的5'非翻译区相关的候选RNA相互作用蛋白。我们确定了SRSF1，一个原型剪接因子，对翻译产生直接和间接的影响。在代表性的雌激素受体阳性和雌激素受体阴性细胞系中，我们发现蛋白质合成在很大程度上依赖于SRSF1。SRSF1主要是核内的。在某些条件下，SRSF1从细胞核转移到与之结合的细胞质MYC和CDK1 mRNA并上调其内部核糖体进入位点介导的翻译。我们的结果指出了剪接和翻译之间的协同作用，并揭示了某些RNA结合蛋白如何调节乳腺癌的翻译前景。