RNA binding proteins drive proliferation and tumorigenesis by regulating the translation and stability of specific subsets of messenger RNAs (mRNAs). We have investigated the role of eukaryotic initiation factor 4B (eIF4B) in this process and identify 10-fold more RNA binding sites for eIF4B in tumour cells from patients with diffuse large B-cell lymphoma compared to control B cells and, using individual-nucleotide resolution UV cross-linking and immunoprecipitation, find that eIF4B binds the entire length of mRNA transcripts. eIF4B stimulates the helicase activity of eIF4A, thereby promoting the unwinding of RNA structure within the 5′ untranslated regions of mRNAs. We have found that, in addition to its well-documented role in mRNA translation, eIF4B additionally interacts with proteins associated with RNA turnover, including UPF1 (up-frameshift protein 1), which plays a key role in histone mRNA degradation at the end of S phase. Consistent with these data, we locate an eIF4B binding site upstream of the stem–loop structure in histone mRNAs and show that decreased eIF4B expression alters histone mRNA turnover and delays cell cycle progression through S phase. Collectively, these data provide insight into how eIF4B promotes tumorigenesis.

中文翻译：

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真核起始因子 4B 是一种调节组蛋白 mRNA 的多功能 RNA 结合蛋白


RNA 结合蛋白通过调节信使 RNA （mRNA） 特定亚群的翻译和稳定性来驱动增殖和肿瘤发生。我们研究了真核起始因子 4B （eIF4B） 在此过程中的作用，并与对照 B 细胞相比，在弥漫性大 B 细胞淋巴瘤患者的肿瘤细胞中鉴定了 eIF4B 的 RNA 结合位点多 10 倍，并且使用单个核苷酸分辨率紫外线交联和免疫沉淀，发现 eIF4B 结合整个长度的 mRNA 转录本。eIF4B 刺激 eIF4A 的解旋酶活性，从而促进 mRNA 的 5' 非翻译区内 RNA 结构的解旋。我们发现，除了在 mRNA 翻译中有据可查的作用外，eIF4B 还与与 RNA 周转相关的蛋白质相互作用，包括 UPF1 （上移码蛋白 1），它在 S 期结束时的组蛋白 mRNA 降解中起关键作用。与这些数据一致，我们在组蛋白 mRNA 中定位了茎环结构上游的 eIF4B 结合位点，并表明 eIF4B 表达降低会改变组蛋白 mRNA 周转并延迟细胞周期进程通过 S 期。总的来说，这些数据为 eIF4B 如何促进肿瘤发生提供了见解。