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

Author

Listed:
  • Christoph Sadée

    (Stanford University School of Medicine)

  • Lauren D. Hagler

    (Stanford University School of Medicine)

  • Winston R. Becker

    (Stanford University School of Medicine)

  • Inga Jarmoskaite

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Pavanapuresan P. Vaidyanathan

    (Stanford University School of Medicine
    Protillion Biosciences)

  • Sarah K. Denny

    (Stanford University School of Medicine
    Scribe Therapeutics)

  • William J. Greenleaf

    (Stanford University School of Medicine
    Stanford University
    Chan Zuckerberg Biohub)

  • Daniel Herschlag

    (Stanford University School of Medicine
    Stanford University
    Stanford University)

Abstract

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.

Suggested Citation

  • Christoph Sadée & Lauren D. Hagler & Winston R. Becker & Inga Jarmoskaite & Pavanapuresan P. Vaidyanathan & Sarah K. Denny & William J. Greenleaf & Daniel Herschlag, 2022. "A comprehensive thermodynamic model for RNA binding by the Saccharomyces cerevisiae Pumilio protein PUF4," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31968-z
    DOI: 10.1038/s41467-022-31968-z
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    References listed on IDEAS

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    1. Beilin Zhang & Maria Gallegos & Alessandro Puoti & Eileen Durkin & Stanley Fields & Judith Kimble & Marvin P. Wickens, 1997. "A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line," Nature, Nature, vol. 390(6659), pages 477-484, December.
    2. Debashish Ray & Hilal Kazan & Kate B. Cook & Matthew T. Weirauch & Hamed S. Najafabadi & Xiao Li & Serge Gueroussov & Mihai Albu & Hong Zheng & Ally Yang & Hong Na & Manuel Irimia & Leah H. Matzat & R, 2013. "A compendium of RNA-binding motifs for decoding gene regulation," Nature, Nature, vol. 499(7457), pages 172-177, July.
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