Decoding ADAR1: Unraveling RNA Editing in Fat Cells and Obesity

Hello! My name is Aashna. Welcome to my introductory blog post! Here, I’d like to talk to you about what excites me about my research project, how I got involved, and provide a bit of background on the biology.

My journey into the UCSF Wang Lab has been a long-winded one – from volunteering at the Sikh Temple medical clinic to connecting with a UCSF post-doc at a medical conference and shadowing under her to conducting a data analysis project under the Principal Investigator this past summer! My overarching goal at this pure-biology lab is to analyze their vast fat cell datasets to give them significance in the context of metabolic research.

One of the lab’s key projects is to understand the mechanism of action of the enzyme ADAR1. ADAR1 is the star of the show in this research project, so make sure to remember that it is an RNA-editing enzyme (operates on double-stranded RNAs (dsRNAs), replacing select “A” nucleotides with “G” nucleotides to mark them as “self”). Its role has been well-explored in viral infections and cancer, but not so much in fat cell biology. That’s where we come in!

This past summer, at the UCSF Wang Lab, I had a lot of spare time as I waited for computationally intensive code segments to run on the lab’s mouse fat data to identify ADAR1’s RNA-editing sites. What else to do with this time than look for public datasets that might complement the lab’s data? So, I found a Finnish human metabolic dataset and analyzed it in different ways. What I definitely was not expecting to find was that the inflammatory pathway, interferon-alpha signaling, regulated by the enzyme ADAR1, is enriched in obesity! Eureka! Doors of possibilities opened for me and the lab about investigating connections between inflammation and obesity!

Armed with the knowledge I gained through last summer’s trial and error exploration of the lab’s data, I now return to the task of statistically analyzing the lab’s data to understand the mechanism of action of ADAR1 in mouse brown and white fat cells by identifying its RNA-editing sites. I hope such results can give us a glimpse into ADAR1’s complex cellular function and how perturbations to its function can contribute to obesity.