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| Item Type: | Preprint |
|---|---|
| Title: | An integrated landscape of mRNA and protein isoforms |
| Creators: |
Kedan, A., Zauber, H.  ORCID: https://orcid.org/0000-0003-2595-1147, Wang, M.R., Zhu, Q., Fang, L. ORCID: https://orcid.org/0000-0003-4502-1756, Chen, W. ORCID: https://orcid.org/0000-0003-3263-1627 and Selbach, M. ORCID: https://orcid.org/0000-0003-2454-8751
|
| Abstract: | Alternative splicing and proteolytic processing expand the functional diversity of the human proteome by generating distinct protein isoforms from a single gene. However, the extent to which transcript isoforms give rise to distinct protein products remains unclear, in part due to technical limitations in proteomic workflows. Here, we combine full-length mRNA sequencing with SDS-PAGE-based protein fractionation and quantitative mass spectrometry to construct an integrated landscape of mRNA and protein isoforms in human RPE-1 cells. To overcome the inherent ambiguity of bottom-up proteomics in isoform detection, we developed IsoFrac, a computational pipeline that resolves protein isoforms based on their migration profiles across gel fractions. This approach enabled the identification of ~45,000 full-length transcripts, ~32,000 ORFs, and ~16,000 distinct protein isoforms. Comparative analyses revealed widespread translation of alternative transcripts and uncovered proteolytic processing as a major, underappreciated source of proteome complexity. Our results establish a scalable framework for isoform-resolved proteogenomics and provide a reference resource for studying the molecular diversity encoded by the human genome. |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2025.04.16.648713 |
| Date: | 19 April 2025 |
| Official Publication: | https://doi.org/10.1101/2025.04.16.648713 |
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