大多数研究cohesin功能的研究都认为Stromalin抗原（STAG / SA）蛋白是核心复合物成员，因为它们与cohesin环的普遍相互作用。在这里，我们提供了功能数据来支持这样的观点，即SA亚单位不仅仅是该结构中的乘客，而是在定位cohesin到不同生物过程和促进在这些位置载入复合物方面发挥关键作用。我们表明，在RAD21急性缺失的细胞中，SA蛋白仍然与染色质结合，聚集在三维中并与CTCF以及涉及多个RNA处理机制的广泛范围的RNA结合蛋白相互作用。因此，SA蛋白即使在没有cohesin的情况下也会与RNA，RNA结合蛋白和R-loop相互作用。我们的结果将SA1置于cohesin环的染色质上游，并揭示了SA1在cohesin载入中的作用，该作用与NIPBL，经典的cohesin载体无关。我们提出SA1利用结构性R-loop平台将cohesin载入和染色质结构与多种功能联系起来。由于SA蛋白是泛癌症靶点，而R-loop在癌症生物学中扮演着越来越普遍的角色，我们的结果对于理解SA蛋白在癌症和疾病中的机制有重要的意义。©2023，Porter等。

Most studies of cohesin function consider the Stromalin Antigen (STAG/SA) proteins as core complex members given their ubiquitous interaction with the cohesin ring. Here, we provide functional data to support the notion that the SA subunit is not a mere passenger in this structure, but instead plays a key role in the localization of cohesin to diverse biological processes and promotes loading of the complex at these sites. We show that in cells acutely depleted for RAD21, SA proteins remain bound to chromatin, cluster in 3D and interact with CTCF, as well as with a wide range of RNA binding proteins involved in multiple RNA processing mechanisms. Accordingly, SA proteins interact with RNA, RNA binding proteins and R-loops, even in the absence of cohesin. Our results place SA1 on chromatin upstream of the cohesin ring and reveal a role for SA1 in cohesin loading which is independent of NIPBL, the canonical cohesin loader. We propose that SA1 takes advantage of structural R-loop platforms to link cohesin loading and chromatin structure with diverse functions. Since SA proteins are pan-cancer targets, and R-loops play an increasingly prevalent role in cancer biology, our results have important implications for the mechanistic understanding of SA proteins in cancer and disease.© 2023, Porter et al.