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The structural basis for RNA selectivity by the IMP family of RNA-binding proteins

Author

Listed:
  • Jeetayu Biswas

    (Albert Einstein College of Medicine)

  • Vivek L. Patel

    (Massachusetts General Hospital)

  • Varun Bhaskar

    (Friedrich Miescher Institute for Biomedical Research)

  • Jeffrey A. Chao

    (Friedrich Miescher Institute for Biomedical Research)

  • Robert H. Singer

    (Albert Einstein College of Medicine
    Janelia Research Campus)

  • Carolina Eliscovich

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

Abstract

The IGF2 mRNA-binding proteins (ZBP1/IMP1, IMP2, IMP3) are highly conserved post-transcriptional regulators of RNA stability, localization and translation. They play important roles in cell migration, neural development, metabolism and cancer cell survival. The knockout phenotypes of individual IMP proteins suggest that each family member regulates a unique pool of RNAs, yet evidence and an underlying mechanism for this is lacking. Here, we combine systematic evolution of ligands by exponential enrichment (SELEX) and NMR spectroscopy to demonstrate that the major RNA-binding domains of the two most distantly related IMPs (ZBP1 and IMP2) bind to different consensus sequences and regulate targets consistent with their knockout phenotypes and roles in disease. We find that the targeting specificity of each IMP is determined by few amino acids in their variable loops. As variable loops often differ amongst KH domain paralogs, we hypothesize that this is a general mechanism for evolving specificity and regulation of the transcriptome.

Suggested Citation

  • Jeetayu Biswas & Vivek L. Patel & Varun Bhaskar & Jeffrey A. Chao & Robert H. Singer & Carolina Eliscovich, 2019. "The structural basis for RNA selectivity by the IMP family of RNA-binding proteins," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12193-7
    DOI: 10.1038/s41467-019-12193-7
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    Cited by:

    1. Xuan Ye & Wen Yang & Soon Yi & Yanan Zhao & Gabriele Varani & Eckhard Jankowsky & Fan Yang, 2023. "Two distinct binding modes provide the RNA-binding protein RbFox with extraordinary sequence specificity," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Tatsuya Yoshizawa & Yoshifumi Sato & Shihab U. Sobuz & Tomoya Mizumoto & Tomonori Tsuyama & Md. Fazlul Karim & Keishi Miyata & Masayoshi Tasaki & Masaya Yamazaki & Yuichi Kariba & Norie Araki & Eiichi, 2022. "SIRT7 suppresses energy expenditure and thermogenesis by regulating brown adipose tissue functions in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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