文章：

RNA结合蛋白对MicroRNA的调控及其对癌症的影响

MicroRNA regulation by RNA-binding proteins and its implications for cancer

原文发布日期：2011-08-05

DOI: 10.1038/nrc3107

类型: Review Article

开放获取: 否

要点：

1. Global downregulation of microRNA (miRNA) expression is an apparent feature of many tumours. Oncogenic or tumour-suppressive functions have been assigned to numerous miRNAs.
2. Alterations in key players of miRNA biogenesis affect mature miRNA levels in a global manner, whereas RNA-binding proteins (RBPs) regulating specific miRNAs can contribute to differences in the production of specific (subsets of) miRNAs.
3. The observation that miRNA binding to target mRNAs can repress gene expression through distinct mechanisms suggests the involvement of accessory proteins, some of which are linked to cancer.
4. Interplay between miRNAs and RBPs on target 3′ untranslated regions can rapidly modulate target expression under specific conditions. Binding of RBPs near miRNA target sites can potentially regulate miRNA function either directly by affecting miRNA binding or indirectly through a switch in RNA secondary structure.
5. The activity of RBPs is temporally and spatially regulated through changes in transcription rate, post-translational modifications and subcellular localization, and is sometimes deregulated in cancer and other diseases.
6. The data discussed in this Review illustrate several examples of mechanisms for miRNA–RBP interplay that could hold true for other miRNAs and RBPs. As some of these mechanisms are linked to oncogenesis, the challenge now is to connect the mechanisms of action to disease by applying state-of-the-art genome-wide approaches.

要点翻译：

1. SWI/SNF染色质重塑复合物的特定亚基失活突变在多种癌症中高频发生，这些亚基包括SNF5（亦称SMARCB1、INI1和BAF47）、ARID1A（亦称BAF250A和SMARCF1）、BAF180（亦称PBRM1）以及BRM/SWI2相关基因1（BRG1；亦称SMARCA4）。
2. 携带Snf5和Brg1基因突变的基因工程小鼠模型证实，至少部分SWI/SNF亚基具有确切的肿瘤抑制活性。
3. SWI/SNF复合物通过利用ATP能量重塑染色质来调控基因表达。
4. 该复合物的核心功能是协调基因表达程序的调控，在细胞谱系分化和维持干细胞多能性过程中发挥关键作用。
5. 最新证据揭示了SWI/SNF复合物功能紊乱后促进肿瘤发生的关键通路。
6. 总体而言，修饰染色质结构的酶类正逐渐被视为肿瘤发生的关键调控因子。表观遗传改变具有可逆性潜能（不同于DNA突变），因此靶向抑制染色质修饰酶可能为癌症治疗带来重要突破。

英文摘要：

Non-protein-coding transcripts have been conserved throughout evolution, indicating that crucial functions exist for these RNAs. For example, microRNAs (miRNAs) have been found to modulate most cellular processes. The protein classes of RNA-binding proteins include essential regulators of miRNA biogenesis, turnover and activity. RNA–RNA and protein–RNA interactions are essential for post-transcriptional regulation in normal development and may be deregulated in disease. In reviewing emerging concepts of the interplay between miRNAs and RNA-binding proteins, we highlight the implications of these complex layers of regulation in cancer initiation and progression.

摘要翻译： 

非蛋白编码转录本在进化过程中得以保留，表明这些RNA具有重要功能。例如，微RNA（miRNA）被发现能调控大多数细胞过程。RNA结合蛋白的蛋白类别包括miRNA生物生成、周转和活性的关键调控因子。RNA-RNA和蛋白-RNA相互作用对正常发育中的转录后调控至关重要，并可能在疾病中发生失调。在回顾miRNA与RNA结合蛋白相互作用的新兴概念时，我们强调了这些复杂调控层在癌症发生和进展中的意义。

原文链接：

MicroRNA regulation by RNA-binding proteins and its implications for cancer