Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart, 00168 Rome, Italy.
Organoids Facility, IRCCS Fondazione Policlinico Universitario Agostino Gemelli, 00168 Rome, Italy.
Biomolecules. 2021 Oct 7;11(10):1475. doi: 10.3390/biom11101475.
Signal transduction pathways transmit the information received from external and internal cues and generate a response that allows the cell to adapt to changes in the surrounding environment. Signaling pathways trigger rapid responses by changing the activity or localization of existing molecules, as well as long-term responses that require the activation of gene expression programs. All steps involved in the regulation of gene expression, from transcription to processing and utilization of new transcripts, are modulated by multiple signal transduction pathways. This review provides a broad overview of the post-translational regulation of factors involved in RNA processing events by signal transduction pathways, with particular focus on the regulation of pre-mRNA splicing, cleavage and polyadenylation. The effects of several post-translational modifications (i.e., sumoylation, ubiquitination, methylation, acetylation and phosphorylation) on the expression, subcellular localization, stability and affinity for RNA and protein partners of many RNA-binding proteins are highlighted. Moreover, examples of how some of the most common signal transduction pathways can modulate biological processes through changes in RNA processing regulation are illustrated. Lastly, we discuss challenges and opportunities of therapeutic approaches that correct RNA processing defects and target signaling molecules.
信号转导途径将从外部和内部线索接收到的信息传递,并产生反应,使细胞能够适应周围环境的变化。信号通路通过改变现有分子的活性或定位来触发快速反应,以及需要激活基因表达程序的长期反应。从转录到新转录本的加工和利用的基因表达调控的所有步骤都受到多个信号转导途径的调节。本综述广泛概述了信号转导途径对 RNA 加工事件涉及的因子的翻译后调控,特别关注对前体 mRNA 剪接、切割和多聚腺苷酸化的调控。强调了几种翻译后修饰(如 SUMO 化、泛素化、甲基化、乙酰化和磷酸化)对许多 RNA 结合蛋白的表达、亚细胞定位、稳定性以及与 RNA 和蛋白质伴侣的亲和力的影响。此外,还举例说明了一些最常见的信号转导途径如何通过改变 RNA 加工调控来调节生物过程。最后,我们讨论了纠正 RNA 加工缺陷和靶向信号分子的治疗方法的挑战和机遇。