1. Structural Biology and Molecular Biophysics

Peptides that Mimic RS repeats modulate phase separation of SRSF1, revealing a reliance on combined stacking and electrostatic interactions

  1. Talia Fargason
  2. Naiduwadura Ivon Upekala De Silva
  3. Erin Powell
  4. Zihan Zhang
  5. Trenton Paul
  6. Jamal Shariq
  7. Steve Zaharias
  8. Jun Zhang  Is a corresponding author
  1. University of Alabama at Birmingham, United States
https://doi.org/10.7554/eLife.84412
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  1. Talia Fargason
  2. Naiduwadura Ivon Upekala De Silva
  3. Erin Powell
  4. Zihan Zhang
  5. Trenton Paul
  6. Jamal Shariq
  7. Steve Zaharias
  8. Jun Zhang
(2023)
Peptides that Mimic RS repeats modulate phase separation of SRSF1, revealing a reliance on combined stacking and electrostatic interactions
eLife 12:e84412.
https://doi.org/10.7554/eLife.84412
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Abstract

Phase separation plays crucial roles in both sustaining cellular function and perpetuating disease states. Despite extensive studies, our understanding of this process is hindered by low solubility of phase-separating proteins. One example of this is found in SR and SR-related proteins. These proteins are characterized by domains rich in arginine and serine (RS domains), which are essential to alternative splicing and in vivo phase separation. However, they are also responsible for a low solubility that has made these proteins difficult to study for decades. Here, we solubilize the founding member of the SR family, SRSF1, by introducing a peptide mimicking RS repeats as a co-solute. We find that this RS-mimic peptide forms interactions similar to those of the protein's RS domain. Both interact with a combination of surface-exposed aromatic residues and acidic residues on SRSF1's RNA Recognition Motifs (RRMs) through electrostatic and cation-pi interactions. Analysis of RRM domains from human SR proteins indicates that these sites are conserved across the protein family. In addition to opening an avenue to previously unavailable proteins, our work provides insight into how SR proteins phase separate and participate in nuclear speckles.

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NMR assignment has been deposited to BMRB (ID: 51299).

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Author details

  1. Talia Fargason

    Department of Chemistry, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6888-0356

  2. Naiduwadura Ivon Upekala De Silva

    Department of Chemistry, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Erin Powell

    Department of Chemistry, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Zihan Zhang

    Department of Chemistry, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Trenton Paul

    Department of Chemistry, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Jamal Shariq

    Department of Chemistry, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Steve Zaharias

    Department of Chemistry, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Jun Zhang

    Department of Chemistry, University of Alabama at Birmingham, Birmingham, United States
    For correspondence
    zhanguab@uab.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5842-7424

Funding

National Science Foundation (MCB2024964)

  • Jun Zhang

National Institutes of Health (R35GM147091)

  • Jun Zhang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2023, Fargason et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Talia Fargason
  2. Naiduwadura Ivon Upekala De Silva
  3. Erin Powell
  4. Zihan Zhang
  5. Trenton Paul
  6. Jamal Shariq
  7. Steve Zaharias
  8. Jun Zhang
(2023)
Peptides that Mimic RS repeats modulate phase separation of SRSF1, revealing a reliance on combined stacking and electrostatic interactions
eLife 12:e84412.
https://doi.org/10.7554/eLife.84412

Share this article

https://doi.org/10.7554/eLife.84412

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