Integrated analysis uncovers post-transcriptional determinants in AML
Gene expression is not solely governed by transcription: multiple post-transcriptional mechanisms regulate the translation of mRNAs into proteins, their stability and their subcellular localization. In acute myeloid leukemia (AML), the global contribution of these processes has remained poorly characterized. In this study, researchers from Institut Cochin, in collaboration with several national and international partners, integrated transcriptomic and proteomic data from 44 AML patients to compute protein-to-mRNA ratios (PTRs), a quantitative parameter summarizing post-transcriptional regulation. They show that PTRs are remarkably conserved across patients, AML subtypes and even across different human tissues, pointing to the existence of fundamental and universal regulatory mechanisms.
A detailed analysis of more than one thousand molecular “proxies” — related to mRNA 5′UTR, coding sequence (CDS) and 3′UTR regions, as well as to protein features — allows the identification of the main determinants of PTR variation. These include translation initiation and elongation efficiency, codon composition, mRNA stability and subcellular localization. Finally, the authors develop POSTCODE, a bioinformatics tool designed to annotate omics datasets (transcriptomics, proteomics and ribosome profiling) using these proxies. POSTCODE reveals post-transcriptional regulatory layers that are often overlooked in standard analyses, opening new perspectives for understanding AML biology and for identifying precision medicine strategies. POSTCODE is provided as a user-friendly web application, requiring no programming skills, and can be applied to any human biological question, well beyond the sole context of AML. The tool is freely accessible at: https://postcode-lab.shinyapps.io/POSTCODE/.
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Khadra E. et al. Integrated analysis of post-transcriptional regulations reveals insights into acute myeloid leukemia. Communications Biology (Nature Portfolio), 2025. https://doi.org/10.1038/s42003-025-09156-8