Inside every cell, RNA molecules help carry genetic instructions and guide the production of proteins. These RNA molecules are not static. They can be chemically modified after they are made, and these modifications can influence how stable the RNA is, how efficiently it is translated into protein, and how genes are regulated. Scientists call this layer of control the epitranscriptome.

Although many RNA modifications have been identified, much less is known about the proteins that add, remove, or interpret these marks. These proteins are known as RNA modifying proteins, or RMPs. Understanding how they function across different tissues and diseases has been a major challenge.

Researchers at Sichuan University performed a large scale analysis of RMPs across 63 human tissues. Luo is affiliated with a major biomedical research institution in China, and the group integrated 378 multiomics datasets, including genomics, bulk and single cell transcriptomics, epitranscriptomics, proteomics, and posttranslational modification data. By combining these data types, the researchers created a broad view of how RNA modifying enzymes are regulated and how they influence gene expression.

Using experimental perturbations, the team examined what happens when specific RMPs are altered. They observed changes in RNA modification patterns and gene expression profiles, showing that RMPs can dynamically reshape cellular programs. Through computational approaches such as nonnegative matrix factorization applied to single cell RNA sequencing datasets, they were able to link specific RMP activity patterns to distinct cell types.

One important example involved acute myeloid leukemia, or AML. The researchers identified ALKBH5, an enzyme that regulates m6A RNA modification, as a key player in leukemia biology. In AML stem cells enriched for ALKBH5, they observed distinct modification patterns, altered translation related pathways, immune signaling changes, and unique ligand receptor interactions. These findings suggest that RNA modifications can influence cancer development by reshaping cellular communication and gene regulation networks.

The team also integrated proteogenomic data to uncover how posttranslational modifications, mutations, and protein interaction networks intersect with RNA modifying enzymes. This systems level view highlights how RMPs are embedded in broader regulatory circuits within the cell.

To make their findings accessible to the research community, the authors developed RMzyme, an online platform that consolidates information about RNA modifying enzymes, their regulatory patterns, and their downstream effects. This resource is designed to help scientists explore how RNA modifications contribute to normal biology and human disease.

Overview of the RMzyme database

This platform includes multiomics datasets collected from 63 human tissues. The RMzyme knowledgebase features three search modules centered ~179 human RNA-modifying proteins (RMPs), offering detailed information concerning the posttranscriptional modification machinery at the cell-type level, the regulators and downstream targeting genes, and the protein and posttranslational modification (PTM) at the site and protein levels. 

By combining multiomics integration with RNA sequencing and computational modeling, this work provides a detailed atlas of RNA modifying enzymes in humans. It opens new avenues for understanding how subtle changes in RNA chemistry can shape cell identity, influence disease progression, and potentially serve as therapeutic targets.

Availability – The curated datasets are available at the download page of the website (https://rh-luo.cn/RMzyme),