A comprehensive thermodynamic model for RNA binding by the Saccharomyces cerevisiae Pumilio protein PUF4

Genomic methods have been valuable for identifying RNA-binding proteins (RBPs) and the genes, pathways, and processes they regulate. Nevertheless, standard motif descriptions cannot be used to predict all RNA targets or test quantitative models for cellular interactions and regulation. We present a...

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Bibliographic Details
Published in:Nature communications Vol. 13; no. 1; pp. 4522 - 15
Main Authors: Sadée, Christoph, Hagler, Lauren D., Becker, Winston R., Jarmoskaite, Inga, Vaidyanathan, Pavanapuresan P., Denny, Sarah K., Greenleaf, William J., Herschlag, Daniel
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 04.08.2022
Nature Publishing Group
Nature Portfolio
Subjects:
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631/45/500
631/45/56
631/57/2272/951
Binding
Binding sites
Fungal Proteins - metabolism
Gene expression
Genes
Genomics
Humanities and Social Sciences
Humans
Mathematical models
multidisciplinary
New technology
Prediction models
Protein Binding
Proteins
Ribonucleic acid
RNA
RNA - metabolism
RNA-binding protein
RNA-Binding Proteins - metabolism
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - metabolism
Science
Science (multidisciplinary)
Thermodynamic models
Thermodynamics
Yeast
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Genomic methods have been valuable for identifying RNA-binding proteins (RBPs) and the genes, pathways, and processes they regulate. Nevertheless, standard motif descriptions cannot be used to predict all RNA targets or test quantitative models for cellular interactions and regulation. We present a complete thermodynamic model for RNA binding to the S. cerevisiae Pumilio protein PUF4 derived from direct binding data for 6180 RNAs measured using the RNA on a massively parallel array (RNA-MaP) platform. The PUF4 model is highly similar to that of the related RBPs, human PUM2 and PUM1, with one marked exception: a single favorable site of base flipping for PUF4, such that PUF4 preferentially binds to a non-contiguous series of residues. These results are foundational for developing and testing cellular models of RNA-RBP interactions and function, for engineering RBPs, for understanding the biophysical nature of RBP binding and the evolutionary landscape of RNAs and RBPs. Traditional genomic methods identify RNA-binding proteins (RBPs) and the genes they regulate, but do not provide predictive models. The authors used an emerging technology to obtain a complete thermodynamic model for RNA binding to the PUF4 RBP.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-31968-z