The exozyme model: A continuum of functionally distinct complexes
The exozyme model: A continuum of functionally distinct complexes
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DOI：
10.1261/rna.2364811
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发表时间：
2011-01-01
期刊：
影响因子：
4.5
通讯作者：
Andrulis, Erik D.
中科院分区：
文献类型：
--
作者：
Kiss, Daniel L.;Andrulis, Erik D.
外体复合体由10到11个亚基组成，参与3‘-gt；5’RNA加工和周转的多个方面。目前的模式规定，一个统一的、化学计量的核心外体，由每个亚基的单个副本组成，在体内执行所有的RNA代谢功能。虽然核心成分在体外已经很好地确定了，但现有的遗传、细胞生物学、蛋白质组和转录组数据提出了这样的问题：单个亚基是否只在复合体内对RNA代谢功能做出贡献。在这里，我们叙述了目前对核心外体模型的理解，并展示了对核心模型的预测，这些预测并不被现有证据所满足。为了解决这种差异，我们提出了外酶假说，这是一个新的模型，规定虽然外体亚基可以并且确实在核心内执行某些功能，但外体亚基和辅因子的亚集也组装成具有不同RNA特异性的组成不同的复合体-外酶-的连续体。Exozyme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节提供了一个新的框架。
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.