Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, Aarhus, Denmark.
Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, Aarhus, Denmark.
Mol Cell. 2024 Oct 3;84(19):3644-3655. doi: 10.1016/j.molcel.2024.08.024.
Mammalian genomes produce an abundance of short RNA. This is, to a large extent, due to the genome-wide and spurious activity of RNA polymerase II (RNAPII). However, it is also because the vast majority of initiating RNAPII, regardless of the transcribed DNA unit, terminates within a ∼3-kb early "pausing zone." Given that the resultant RNAs constitute both functional and non-functional species, their proper sorting is critical. One way to think about such quality control (QC) is that transcripts, from their first emergence, are relentlessly targeted by decay factors, which may only be avoided by engaging protective processing pathways. In a molecular materialization of this concept, recent progress has found that both "destructive" and "productive" RNA effectors assemble at the 5' end of capped RNA, orchestrated by the essential arsenite resistance protein 2 (ARS2) protein. Based on this principle, we here discuss early QC mechanisms and how these might sort short RNAs to their final fates.
哺乳动物基因组产生大量的短 RNA。这在很大程度上是由于 RNA 聚合酶 II(RNAPII)的全基因组和偶然活性。然而,这也是因为绝大多数起始的 RNAPII,无论转录的 DNA 单位如何,都在大约 3kb 的早期“暂停区”内终止。鉴于产生的 RNA 构成了功能性和非功能性的物种,它们的正确分类是至关重要的。一种思考这种质量控制 (QC) 的方法是,从第一次出现开始,转录本就被降解因子无情地靶向,只有通过参与保护处理途径才能避免这种情况。在这个概念的分子体现中,最近的进展发现,“破坏性”和“有生产力”的 RNA 效应子都在帽状 RNA 的 5' 端组装,由必需的亚砷酸盐抗性蛋白 2 (ARS2) 蛋白协调。基于这一原则,我们在这里讨论早期 QC 机制以及这些机制如何将短 RNA 分类到它们的最终命运。