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Dr. Yuval Malka, PhD[/caption]
MedicalResearch.com Interview with
Dr. Yuval Malka, PhD
Faculty of Medicine Hebrew University and
Founder & CEO of Modular Therapeutics BV and
Dr. William Faller PhD
University of Bristol
discussing their new study on RNA dicing — a fundamental mechanism that generates multiple functional protein outputs from a single mRNA molecule — and its implications for cancer biology and therapeutics.
MedicalResearch.com: What is the background for this study?
Response: This study is a follow-up to previous work published in recent years (Malka et al., Nature Communications 2017; Malka et al., Molecular Cell 2022), in which we discovered that the mRNA of thousands of genes can be further processed into smaller fragments that translate into shorter proteins. On one hand, this finding helps bridge the gap between our understanding of the transcriptome - traditionally limited to ~20,000 genes and the proteome, which contains hundreds of thousands to potentially millions of distinct protein and peptide isoforms. On the other hand, those earlier studies did not provide sufficient biological insight into this extensive and robust process.
The current study represents the third part of this trilogy, introducing a new concept in RNA biology termed "RNA dicing." We show that RNA dicing in eukaryotic systems enables the production of multiple functional protein outputs from a single mRNA molecule. How does this work? Most proteins consist of several domains, each with a distinct function, for example, mediating protein–protein interactions, determining subcellular localization, or carrying catalytic activity. We demonstrate that RNA dicing selectively removes portions of the mRNA template, resulting in the translation of shorter proteins lacking specific domains. This leads to substantial changes in protein function, localization, and interaction partners. In simple terms, RNA dicing mediates modular gene expression.