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

Qiu, Chen, McCann, Kathleen L., Wine, Robert N., Baserga, Susan J., Hall, Traci M. Tanaka
Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.52 pp. 18554-18559
DNA, RNA-binding proteins, double-stranded RNA, feminization, humans, messenger RNA, nucleotide sequences, translation (genetics), yeasts
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 ā€œLā€-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.