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

• Published in: Molecular cell 2016-11, Vol.64 (3), p.607-615
• Main Authors: Raman, Nithya, Weir, Elisabeth, Müller, Stefan
• Format: Article
• Language: English
• Subjects: AAA+ ATPase; Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; ATPases Associated with Diverse Cellular Activities; Binding Sites; Cloning, Molecular; Co-Repressor Proteins - genetics; Co-Repressor Proteins - metabolism; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - metabolism; Escherichia coli - genetics; Escherichia coli - metabolism; Gene Expression; Gene Expression Regulation; HEK293 Cells; HeLa Cells; Humans; MDN1; PELP1; Protein Binding; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; ribosome biogenesis; ribosome maturation; Ribosome Subunits, Large, Eukaryotic - genetics; Ribosome Subunits, Large, Eukaryotic - metabolism; Ribosome Subunits, Large, Eukaryotic - ultrastructure; SENP3; Signal Transduction; Small Ubiquitin-Related Modifier Proteins - genetics; Small Ubiquitin-Related Modifier Proteins - metabolism; SUMO; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2016.09.039

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. [Display omitted] •PELP1 and the AAA ATPase MDN1 interact in a SUMO-dependent manner•SUMOylation of PELP1 facilitates the recruitment of MDN1 to pre-60S ribosomes•PELP1 deSUMOylation by SENP3 releases PELP1 and MDN1 from pre-60S particles•Balanced SUMO conjugation/deconjugation regulates mammalian pre-ribosome remodeling Raman et al. demonstrate transient SUMO-dependent complex formation between the AAA ATPase MDN1 and PELP1 during 60S biogenesis. They show that SUMO conjugation to PELP1 recruits MDN1 to pre-60S particles, while reversal of this modification by SENP3 is needed for the release of both factors during mammalian pre-ribosome remodeling.