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| Item Type: | Article |
|---|---|
| Title: | An integrated landscape of mRNA and protein isoforms |
| Creators: |
Kedan, Amir, Zauber, Henrik |
| Abstract: | Alternative splicing and proteolytic processing expand proteome diversity by generating distinct protein isoforms from a single gene. However, the relationship between transcript isoforms and protein products remains poorly understood because of limitations in current proteomic workflows. Here, we combined full-length mRNA sequencing with protein fractionation and quantitative mass spectrometry to generate an integrated landscape of mRNA and protein isoforms in human RPE-1 cells. To overcome the ambiguity of bottom-up proteomics, we developed IsoFrac, a computational pipeline that resolves protein isoforms from molecular-weight-resolved peptide migration profiles. Using this approach, we identified ∼45,000 full-length transcripts, ∼32,000 open reading frames (ORFs), and ∼14,000 protein isoform candidates. Comparative analyses revealed widespread translation of alternative transcripts and identified shorter protein variants, likely arising from proteolytic processing and/or alternative translation, as a major and underappreciated source of proteome complexity. Our results establish a scalable framework for isoform-resolved proteogenomics and provide a resource for studying protein isoform diversity. |
| Source: | Cell Reports |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 45 |
| Number: | 9 |
| Page Range: | 117898 |
| Number of Pages: | 1 |
| Date: | 22 September 2026 |
| Official Publication: | https://doi.org/10.1016/j.celrep.2026.117898 |
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