title: A divergent Pumilio repeat protein family for pre-rRNA processing and mRNA localization.
abstract: Pumilio/feminization of XX and XO animals (fem)-3 mRNA-binding factor (PUF) proteins bind sequence specifically to mRNA targets using a single-stranded RNA-binding domain comprising eight Pumilio (PUM) repeats. PUM repeats have now been identified in proteins that function in pre-rRNA processing, including human Puf-A and yeast Puf6. This is a role not previously ascribed to PUF proteins. Here we present crystal structures of human Puf-A that reveal a class of nucleic acid-binding proteins with 11 PUM repeats arranged in an "L"-like shape. In contrast to classical PUF proteins, Puf-A forms sequence-independent interactions with DNA or RNA, mediated by conserved basic residues. We demonstrate that equivalent basic residues in yeast Puf6 are important for RNA binding, pre-rRNA processing, and mRNA localization. Thus, PUM repeats can be assembled into alternative folds that bind to structured nucleic acids in addition to forming canonical eight-repeat crescent-shaped RNA-binding domains found in classical PUF proteins.
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709; and.
authors.forename: Chen
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Departments of Genetics.
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: McCann
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709; and.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Wine
authors.affiliation: Departments of Genetics, Molecular Biophysics and Biochemistry, and Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520 hall4@niehs.nih.gov susan.baserga@yale.edu.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Baserga
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709; and hall4@niehs.nih.gov susan.baserga@yale.edu.
authors.forename: Traci M Tanaka
authors.initials: TM
authors.lastname: Hall
mesh_terms: D020816:Amino Acid Motifs; D018360:Crystallography, X-Ray; D006801:Humans; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012322:RNA Precursors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012331:RNA, Fungal / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C471242:PUM1 protein, human; C487800:Puf6 protein, S cerevisiae; D012322:RNA Precursors; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins
keywords: Puf-A; Puf6; crystal structure; mRNA localization; ribosome biogenesis