An integrated landscape of mRNA and protein isoforms.

Integration of full-length mRNA sequencing and proteomics reveals approximately 14,000 protein isoforms in human cells, highlighting extensive proteome diversity.

• Why it matters: Understanding how transcript isoforms translate into distinct protein variants is crucial for comprehending cellular complexity and disease mechanisms, yet current methods lack resolution.
• What they did: The study combined long-read mRNA sequencing with protein fractionation and developed IsoFrac, a computational pipeline, to identify and resolve protein isoforms from human RPE-1 cells, detecting thousands of transcripts and isoforms.
• The result: The findings show widespread translation of alternative transcripts and uncover shorter protein variants from proteolytic processing or alternative translation, providing a scalable framework for isoform-resolved proteogenomics.