Project Grant RC2DK139552

This $4,087,560 five-year Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under CFDA 93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research aims to develop a comprehensive database of functionally important RNA modifications in key metabolic tissues related to type 2 diabetes and obesity. The prime awardee, Joslin Diabetes Center, will work with sub-awardees at the University of Pennsylvania, University of Chicago, and University of Kentucky to:

1. Perform high-throughput sequencing to map mRNA and chromatin-associated RNA modifications, specifically N6-adenosine methylation (m6A) and pseudouridylation, in human islet, adipose, liver, and skeletal muscle tissues from patients with type 2 diabetes and obesity.

2. Conduct m6A and pseudouridine quantitative trait locus (QTL) studies in these tissues and validate the functional relevance of key RNA modifications through in vitro studies.

3. Interrogate transcription and enhancer activity using ATAC-seq in the metabolic tissues and perform expression QTL analyses to correlate with the RNA modification data.

4. Develop a large-scale resource database on mRNA and chromatin-associated RNA modifications and transcription activity for the broader scientific community.

This comprehensive effort seeks to advance the understanding of epitranscriptomic regulation in human metabolic disorders and provide a valuable data resource to facilitate future basic and translational research.