PAXT-1 promotes XRN2 activity by stabilizing it through a conserved domain.

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.

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