Instituto Leloir, IIBBA-CONICET, C1405BWE, Buenos Aires, Argentina.
RNA Biol. 2011 Nov-Dec;8(6):954-9. doi: 10.4161/rna.8.6.17336. Epub 2011 Nov 1.
Alternative splicing (AS) allows the production of multiple mRNA variants from a single gene, which contributes to increase the complexity of the proteome. There is evidence that AS is regulated not only by auxiliary splicing factors, but also by components of the core spliceosomal machinery, as well as through epigenetic modifications. However, to what extent these different mechanisms contribute to the regulation of AS in response to endogenous or environmental stimuli is still unclear. Circadian clocks allow organisms to adjust physiological processes to daily changes in environmental conditions. Here we review recent evidence linking circadian clock and AS, and discuss the role of Protein Arginine Methyltransferase 5 (PRMT5) in these processes. We propose that the interactions between daily oscillations in AS and circadian rhythms in the expression of splicing factors and epigenetic regulators offer a great opportunity to dissect the contribution of these mechanisms to the regulation of AS in a physiologically relevant context.
可变剪接(AS)允许从单个基因产生多个 mRNA 变体,从而增加蛋白质组的复杂性。有证据表明,AS 的调控不仅依赖于辅助剪接因子,还依赖于核心剪接体机器的组成部分,以及通过表观遗传修饰。然而,这些不同的机制在多大程度上有助于响应内源性或环境刺激调节 AS 仍不清楚。生物钟使生物体能够根据环境条件的日常变化来调整生理过程。在这里,我们回顾了最近将生物钟与 AS 联系起来的证据,并讨论了精氨酸甲基转移酶 5(PRMT5)在这些过程中的作用。我们提出,AS 的日常波动与剪接因子和表观遗传调节剂表达的昼夜节律之间的相互作用为剖析这些机制在生理相关背景下对 AS 调控的贡献提供了很好的机会。