PDF(Pubmed)
Abstract：
Post-transcriptional regulation by RNA binding proteins can determine gene expression levels and drive changes in cancer cell proteomes. Identifying mechanisms of protein-RNA binding, including preferred sequence motifs bound in vivo, provides insights into protein-RNA networks and how they impact mRNA structure, function, and stability. In this review, we will focus on proteins that bind to AU-rich elements (AREs) in nascent or mature mRNA where they play roles in response to stresses encountered by cancer cells. ARE-binding proteins (ARE-BPs) specifically impact alternative splicing, stability, decay and translation, and formation of RNA-rich biomolecular condensates like cytoplasmic stress granules (SGs). For example, recent findings highlight the role of ARE-BPs - like TIAR and HUR - in chemotherapy resistance and in translational regulation of mRNAs encoding pro-inflammatory cytokines. We will discuss emerging evidence that different modes of ARE-BP activity impact leukaemia and lymphoma development, progression, adaptation to microenvironment and chemotherapy resistance.
摘要：
RNA结合蛋白的转录后调节可以决定基因表达水平并驱动癌细胞蛋白质组的变化。鉴定蛋白质-RNA结合的机制，包括体内结合的优选序列基序，提供了对蛋白质-RNA网络以及它们如何影响mRNA结构的见解，函数,和稳定性。在这次审查中,我们将重点关注与新生或成熟mRNA中富含AU的元件（ARE）结合的蛋白质，它们在响应癌细胞遇到的压力中发挥作用。ARE结合蛋白（ARE-BPs）特异性影响可变剪接，稳定性,衰变和翻译，和形成富含RNA的生物分子缩合物，如胞质应激颗粒（SGs）。例如,最近的研究结果强调了ARE-BPs-如TIAR和HUR-在化疗耐药和编码促炎细胞因子的mRNA翻译调节中的作用.我们将讨论新出现的证据，即不同的ARE-BP活动模式影响白血病和淋巴瘤的发展，programming,适应微环境和化疗抗性。
