2. Academic Validation
  3. A divergent Pumilio repeat protein family for pre-rRNA processing and mRNA localization

A divergent Pumilio repeat protein family for pre-rRNA processing and mRNA localization

  • Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18554-9. doi: 10.1073/pnas.1407634112.
Chen Qiu 1,  Kathleen L McCann 2,  Robert N Wine 1,  Susan J Baserga 3,  Traci M Tanaka Hall 4
Affiliations

Affiliations

  • 1 Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709; and.
  • 2 Departments of Genetics.
  • 3 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.
  • 4 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.
PMID: 25512524 DOI: 10.1073/pnas.1407634112
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.

Keywords

Puf-A; Puf6; crystal structure; mRNA localization; ribosome biogenesis.

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