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  1. Home
  2. Systematic Analysis Of The Effects Of Splicing On The Diversity Of Post-translational Modifications In Protein Isoforms Using Ptm-pose.
  1. Home
  2. Systematic Analysis Of The Effects Of Splicing On The Diversity Of Post-translational Modifications In Protein Isoforms Using Ptm-pose.

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Systematic analysis of the effects of splicing on the diversity of post-translational modifications in protein

Sam Crowl1, Maeve Bella Coleman1, Andrew Chaphiv1

  • 1Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22903, USA; Department of Genome Sciences, University of Virginia, Charlottesville, VA 22903, USA.

Cell Systems
|June 13, 2025

View abstract on PubMed

Summary
This summary is machine-generated.

We developed PTM-POSE to analyze how protein modifications and splicing interact. Our tool reveals how splicing diversifies post-translational modifications (PTMs) across protein isoforms, impacting their function.

Keywords:
ESRP1SGKalternative splicingcancerlinear motifsphosphorylationpost-translational modificationsprotein isoforms

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Area of Science:

  • Molecular Biology
  • Bioinformatics
  • Proteomics

Background:

  • Post-translational modifications (PTMs) and alternative splicing are critical regulatory mechanisms governing protein function.
  • Understanding the interplay between PTMs and splicing is essential for elucidating complex cellular processes.
  • Existing tools lack comprehensive analysis of the combined effects of these regulatory events.

Purpose of the Study:

  • To develop and present PTM-POSE, a novel computational tool designed to explore the relationship between PTMs and splicing.
  • To identify and analyze how alternative splicing events influence PTM site occurrence and regulation across protein isoforms.
  • To provide a resource for investigating the functional consequences of splicing-PTM interplay on protein interactions and enzymatic activity.

Main Methods:

  • Development of PTM-POSE, a projection method to map PTM sites onto splice events using Ensembl transcript data.
  • Systematic analysis of large-scale transcriptomic data to identify splicing-driven PTM variations.
  • Experiment-specific analysis of PTM-associated splicing events to infer network rewiring.

Main Results:

  • PTM-POSE successfully identifies potential PTM sites linked to alternative splicing and isoforms.
  • Splicing diversifies PTMs across isoforms through PTM site exclusion (32%) or alteration of flanking sequences (2%).
  • Analysis revealed potential rewiring of protein-interaction and kinase-substrate networks, indicating coordinated PTM signaling.

Conclusions:

  • PTM-POSE provides a powerful framework for dissecting the complex relationship between splicing and PTMs.
  • Splicing plays a significant role in diversifying PTM landscapes, thereby expanding proteome complexity and regulatory potential.
  • The tool and data are publicly available to facilitate further research into splicing-PTM networks and their functional implications.