Role of mRNA internal 2′-O methylation in post-transcriptional regulation

Yang Yi, PhD, assistant professor of Urology, received a new grant from the National Institute of General Medical Sciences at the National Institutes of Health (NIH) to better understand a new layer of gene regulation.  

Tell me about the grant you received. (The source, the $ amount, etc.) 

I was recently awarded a Maximizing Investigators’ Research Award (MIRA), an R35 grant from the National Institute of General Medical Sciences at the NIH that supports early-stage investigators. The award provides approximately $2.2 million over five years, including both direct and indirect costs, to support my lab’s research program. 

What are the aims of the project?  

Rather than focusing on a single question, our research program aims to understand how a relatively understudied RNA modification called 2′-O-methylation controls gene expression and cell behavior. 

We are particularly interested in three areas: first, identifying the proteins that interact with or are influenced by this modification; second, understanding how it works together with other RNA modifications to fine-tune gene regulation; and third, exploring how these processes shape cell identity, especially during differentiation. Together, this work will define a new layer of gene regulation that has been largely overlooked. 

What are your next steps? 

Our immediate next steps are to systematically map where these RNA modifications occur across the transcriptome and identify the proteins and pathways they influence. We will also use advanced sequencing technologies and functional assays to understand how these modifications affect RNA stability, splicing and protein production. 

In parallel, we will extend these studies into biologically relevant systems, including models of cell differentiation, to understand how these mechanisms contribute to changes in cell identity. This combination of mechanistic and systems-level approaches will allow us to move from discovery to functional insight. 

What do you hope will come out of this funded research? 

We hope this work will uncover fundamentally new principles of gene regulation by revealing how RNA modifications coordinate with each other and with protein regulators to control cell behavior. In the long term, these insights could lead to new biomarkers and therapeutic strategies, particularly for diseases like cancer where gene regulation is disrupted. More broadly, we aim to establish this area of RNA biology as an important framework for understanding how cells make decisions in both health and disease. 

Learn more about the project here.