Year: 2026
Type: article
Abstract: RNA modifications represent a dynamic layer of gene expression regulation, RNA stability, and translation with profound implications for cellular function and disease. However, the critical regulation and functions of RNA-modifying proteins (RMPs) remain poorly understood. Here, we present a large-scale characterization of RMPs through 378 multiomics datasets encompassing genomics, bulk and single-cell transcriptomics, epitranscriptomics, proteomics, and posttranslational modifications (PTMs) across 63 human tissues. Our analysis of experimental perturbations of RMPs revealed dynamic differential modification peaks and expressed genes. We applied nonnegative matrix factorization to annotate RMP-mediated cell types in single-cell transcriptomes. Functional annotations in acute myeloid leukemia (AML) revealed RMPs such as ALKBH5 as critical mediators of m6A dynamics, influencing pathways involved in translation initiation, immune regulation, and tumorigenesis. We revealed cell type-specific modification patterns, including those in ALKBH5-enriched AML stem cells with special ligand‒receptor interactions and genetic variations modulated by m6A. We integrated proteogenomic data to uncover PTM-associated regulatory, mutation, and protein‒protein interaction networks linked to RMPs. We developed RMzyme, a platform that consolidates our findings and provides insights into RMPs and their downstream effects. This resource is expected to facilitate biomedical research into the molecular mechanisms of human diseases through the lens of RNA modifications and multiomics data integration.
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,790
Funders: National Science Foundation, Cancer Prevention and Research Institute of Texas, University of Texas Health Science Center at Houston, National Natural Science Foundation of China, Sichuan University, National Institutes of Health, National Major Science and Technology Projects of China, West China Hospital, Sichuan University, National Cancer Institute
Awards: An integrated imaging informatics platform for HCC surveillance, G291053052, Optimizing mRNA sequences with deep neural networks, G6919112675, Developing novel machine learning approaches to studying cell development, Developing Random Field based novel approaches for spatial transcriptomics, Multiscale Resolution and Deep Network Approaches for Deconvolving Different Cell Types in Bulk Tumor using Single-cell Sequencing Data (scDEC), Developing mRNAdesigner tool package for optimization of mRNA sequence, Microbial-based platform for assessing organ damage in alcohol use disorders (AUD)
OpenAlex ID: W7128625345