PAXT-1 通过其保守结构域稳定 XRN2，从而促进其活性。
PAXT-1 promotes XRN2 activity by stabilizing it through a conserved domain.
机构信息
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
出版信息
Mol Cell. 2014 Jan 23;53(2):351-60. doi: 10.1016/j.molcel.2014.01.001.
XRN2 is an essential eukaryotic exoribonuclease that processes and degrades various substrates. Here we identify the previously uncharacterized protein R05D11.6/PAXT-1 as a subunit of an XRN2 complex in C. elegans. Targeted paxt-1 inactivation through TALEN-mediated genome editing reduces XRN2 levels, decreases miRNA turnover activity, and results in worm death, which can be averted by overexpressing xrn-2. Hence, stabilization of XRN2 is a major function of PAXT-1. A truncated PAXT-1 protein retaining a predicted domain of unknown function (DUF3469) suffices to restore viability to paxt-1 mutant animals, elevates XRN2 levels, and binds to XRN2. This domain occurs in additional metazoan proteins and mediates interaction of human CDKN2AIP/CARF and NKRF/NRF with XRN2. Thus, we have identified a bona fide XRN2-binding domain (XTBD) that can link different proteins, and possibly functionalities, to XRN2.
XRN2 是一种必需的真核外切核酸酶，可加工和降解各种底物。在这里，我们鉴定了先前未被表征的蛋白质 R05D11.6/PAXT-1 作为秀丽隐杆线虫 XRN2 复合物的一个亚基。通过 TALEN 介导的基因组编辑靶向性灭活 paxt-1 会降低 XRN2 水平，降低 miRNA 周转活性，并导致线虫死亡，而过表达 xrn-2 可以避免这种情况。因此，XRN2 的稳定是 PAXT-1 的主要功能。保留预测的未知功能结构域（DUF3469）的截断 PAXT-1 蛋白足以恢复 paxt-1 突变体动物的活力，提高 XRN2 水平，并与 XRN2 结合。该结构域存在于其他后生动物蛋白中，并介导人类 CDKN2AIP/CARF 和 NKRF/NRF 与 XRN2 的相互作用。因此，我们已经鉴定出一个真正的 XRN2 结合结构域（XTBD），它可以将不同的蛋白质和可能的功能连接到 XRN2 上。
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