The AAA ATPase MDN1 Acts as a SUMO-Targeted Regulator in Mammalian Pre-ribosome Remodeling

Biogenesis of translation-competent 80S ribosomes is a multi-step process requiring the sequential action of non-ribosomal trans-acting factors. We previously identified the human PELP1-TEX10-WDR18 complex and the associated SUMO isopeptidase SENP3 as regulators of 60S maturation. We provided evidence that deconjugating SUMO from PELP1 by SENP3 is instrumental for proper ribosome biogenesis. Here we show that SUMO conjugation/deconjugation of PELP1 controls its dynamic association with the AAA ATPase MDN1, a key factor of pre-60S remodeling. We demonstrate that modification of PELP1 promotes the recruitment of MDN1 to pre-60S particles, while deSUMOylation is needed to release both MDN1 and PELP1 from pre-ribosomes. Inactivation of SENP3 traps MDN1 at pre-60S particles and prevents critical remodeling events, ultimately generating aberrant pre-60S complexes. We define MDN1 as a SUMO-targeted AAA ATPase, and we propose that a controlled SUMO cycle on PELP1 serves as regulatory point for mammalian 60S maturation through ordered recruitment and release of MDN1.