title: The SMC Loader Scc2 Promotes ncRNA Biogenesis and Translational Fidelity.
abstract: The Scc2-Scc4 complex is essential for loading the cohesin complex onto DNA. Cohesin has important roles in chromosome segregation, DSB repair, and chromosome condensation. Here we report that Scc2 is important for gene expression in budding yeast. Scc2 and the transcriptional regulator Paf1 collaborate to promote the production of Box H/ACA snoRNAs which guide pseudouridylation of RNAs including ribosomal RNA. Mutation of SCC2 was associated with defects in the production of ribosomal RNA, ribosome assembly, and splicing. While the scc2 mutant does not have a general defect in protein synthesis, it shows increased frameshifting and reduced cap-independent translation. These findings suggest Scc2 normally promotes a gene expression program that supports translational fidelity. We hypothesize that translational dysfunction may contribute to the human disorder Cornelia de Lange syndrome, which is caused by mutations in NIPBL, the human ortholog of SCC2.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America; Universite Pierre et Marie Curie (Paris VI), Paris, France.
authors.forename: Musinu
authors.initials: M
authors.lastname: Zakari
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Trimble Ross
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
authors.forename: Allison
authors.initials: A
authors.lastname: Peak
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
authors.forename: Marco
authors.initials: M
authors.lastname: Blanchette
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
authors.forename: Chris
authors.initials: C
authors.lastname: Seidel
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America; Department of Biochemistry and Molecular Biology, University of Kansas School of Medicine, Kansas City, Kansas, United States of America.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gerton
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics; D002843:Chromatin / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis* / Q000235:genetics; D003635:De Lange Syndrome / Q000235:genetics* / Q000473:pathology; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D012335:RNA, Ribosomal / Q000096:biosynthesis / Q000235:genetics; D020537:RNA, Small Nucleolar / Q000096:biosynthesis / Q000235:genetics; D012270:Ribosomes / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D011506:Proteins; D062085:RNA, Long Noncoding; D012335:RNA, Ribosomal; D020537:RNA, Small Nucleolar; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C487465:NIPBL protein, human; C410592:SCC2 protein, S cerevisiae