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.
- National Inst. of Health, Research Triangle Park, NC (United States). National Inst. of Environmental Health Sciences. Epigenetics and Stem Cell Biology Lab.
- Yale Univ., New Haven, CT (United States). School of Medicine. Dept. of Genetics
- 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:
- Grant/Contract Number:
- AC02-05CH11231; W-31-109-Eng-38; GM52581
- 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
- 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
- 60 APPLIED LIFE SCIENCES; Puf-A; crystal structure; Puf6; ribosome biogenesis; mRNA localization
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