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

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. In this paper 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. Finally, 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:
 [1] ;  [2] ;  [1] ;  [3] ;  [1]
  1. National Inst. of Health, Research Triangle Park, NC (United States). National Inst. of Environmental Health Sciences. Epigenetics and Stem Cell Biology Lab.
  2. Yale Univ., New Haven, CT (United States). School of Medicine. Dept. of Genetics
  3. Yale Univ., New Haven, CT (United States). School of Medicine. Dept. of Genetics. Dept. of Molecular Biophysics and Biochemistry. Dept. of Therapeutic Radiology
Publication Date:
OSTI Identifier:
1170010
Grant/Contract Number:
AC02-05CH11231; W-31-109-Eng-38; GM52581
Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 111; Journal Issue: 52; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Research Org:
Yale Univ., New Haven, CT (United States). School of Medicine; National Inst. of Health, Research Triangle Park, NC (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health (NIH) (United States)
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES; Puf-A; crystal structure; Puf6; ribosome biogenesis; mRNA localization