Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
Curr Opin Genet Dev. 2022 Feb;72:38-44. doi: 10.1016/j.gde.2021.10.008. Epub 2021 Nov 22.
Scaffold attachment factor A (SAF-A) or hnRNP U is a nuclear RNA-binding protein with a well-documented role in processing newly transcribed RNA. Recent studies also indicate that SAF-A can oligomerise in an ATP-dependent manner and interact with RNA to form a dynamic nuclear mesh. This mesh is thought to regulate nuclear and chromatin architecture, yet a mechanistic understanding is lacking. Here, we review developments in the field to understand how the SAF-A/RNA mesh affects chromatin organisation in interphase and mitosis. As SAF-A has an intrinsically disordered domain we discuss how the chromatin mesh is related to nuclear phase-separated condensates, which in other situations have been shown to regulate transcription and cell functions. Finally, we infer possible links between diseases emerging from SAF-A mutations and its role in chromatin organisation and regulation.
支架附着因子 A(SAF-A)或 hnRNP U 是一种核 RNA 结合蛋白,其在加工新转录的 RNA 方面具有明确的作用。最近的研究还表明,SAF-A 可以以 ATP 依赖性方式寡聚化,并与 RNA 相互作用形成动态核网格。据认为,该网格可调节核和染色质结构,但缺乏对其机制的理解。在这里,我们回顾了该领域的发展,以了解 SAF-A/RNA 网格如何影响间期和有丝分裂中的染色质组织。由于 SAF-A 具有固有无序结构域,我们讨论了染色质网格与核相分离凝聚物的关系,在其他情况下,已经表明该凝聚物可调节转录和细胞功能。最后,我们推断出由 SAF-A 突变引起的疾病与其在染色质组织和调控中的作用之间可能存在的联系。