title: LAS1L interacts with the mammalian Rix1 complex to regulate ribosome biogenesis.
abstract: The coordination of RNA polymerase I transcription with pre-rRNA processing, preribosomal particle assembly, and nuclear export is a finely tuned process requiring the concerted actions of a number of accessory factors. However, the exact functions of some of these proteins and how they assemble in subcomplexes remain poorly defined. LAS1L was first described as a nucleolar protein required for maturation of the 60S preribosomal subunit. In this paper, we demonstrate that LAS1L interacts with PELP1, TEX10, and WDR18, the mammalian homologues of the budding yeast Rix1 complex, along with NOL9 and SENP3, to form a novel nucleolar complex that cofractionates with the 60S preribosomal subunit. Depletion of LAS1L-associated proteins results in a p53-dependent G1 arrest and leads to defects in processing of the pre-rRNA internal transcribed spacer 2 region. We further show that the nucleolar localization of this complex requires active RNA polymerase I transcription and the small ubiquitin-like modifier-specific protease SENP3. Taken together, our data identify a novel mammalian complex required for 60S ribosomal subunit synthesis, providing further insight into the intricate, yet poorly described, process of ribosome biogenesis in higher eukaryotes.
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, TX 77030, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Castle
authors.forename: Erica K
authors.initials: EK
authors.lastname: Cassimere
authors.forename: Catherine
authors.initials: C
authors.lastname: Denicourt
mesh_terms: D002466:Cell Nucleolus / Q000378:metabolism; D056970:Co-Repressor Proteins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011116:Polynucleotide 5'-Hydroxyl-Kinase / Q000378:metabolism; D054683:Ribosome Subunits, Large, Eukaryotic / Q000378:metabolism*; D058207:Sumoylation; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D056970:Co-Repressor Proteins; C552426:Las1L protein, human; D009687:Nuclear Proteins; C438485:PELP1 protein, human; C558247:TEX10 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C558249:WDR18 protein, human; D011116:Polynucleotide 5'-Hydroxyl-Kinase; C554920:NOL9 protein, human; D003546:Cysteine Endopeptidases; C499718:SENP3 protein, human