Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4960, USA.
RNA. 2011 Jan;17(1):1-13. doi: 10.1261/rna.2364811. Epub 2010 Nov 10.
Exosome complexes are composed of 10 to 11 subunits and are involved in multiple facets of 3' → 5' RNA processing and turnover. The current paradigm stipulates that a uniform, stoichiometric core exosome, composed of single copies of each subunit, carries out all RNA metabolic functions in vivo. While core composition is well established in vitro, available genetic, cell biological, proteomic, and transcriptomic data raise questions about whether individual subunits contribute to RNA metabolic functions exclusively within the complex. Here, we recount the current understanding of the core exosome model and show predictions of the core model that are not satisfied by the available evidence. To resolve this discrepancy, we propose the exozyme hypothesis, a novel model stipulating that while exosome subunits can and do carry out certain functions within the core, subsets of exosome subunits and cofactors also assemble into a continuum of compositionally distinct complexes--exozymes--with different RNA specificities. The exozyme model is consistent with all published data and provides a new framework for understanding the general mechanisms and regulation of RNA processing and turnover.
外核体复合物由 10 到 11 个亚基组成，参与 3' → 5' RNA 加工和周转的多个方面。目前的模式规定，由每个亚基的单个拷贝组成的统一、化学计量的核心外核体，在体内执行所有 RNA 代谢功能。虽然核心组成在体外已经得到很好的确立，但现有的遗传、细胞生物学、蛋白质组学和转录组学数据提出了这样的问题，即单个亚基是否仅在复合物内有助于 RNA 代谢功能。在这里，我们回顾了核心外核体模型的现有理解，并展示了核心模型的预测，这些预测与现有证据不符。为了解决这一差异，我们提出了外切酶假说，这是一个新的模型，规定虽然外核体亚基可以并且确实在核心内执行某些功能，但外核体亚基和辅助因子的子集也会组装成具有不同 RNA 特异性的组成上不同的复合物——外切酶——的连续体。外切酶模型与所有已发表的数据一致，并为理解 RNA 加工和周转的一般机制和调控提供了一个新的框架。
