Anindya Dutta, MBBS, Ph.D.Anindya Dutta, MBBS, Ph.D., chair of the Department of Genetics, is the latest winner of the Heersink School of Medicine’s Featured Discovery. This initiative celebrates important research from Heersink faculty members.
Dutta’s study, “TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer,” was recently published in Nature Communications.
“Our latest work investigates how an intricate modification affects small RNA functions. We found bladder cancer cells could be using RNA modification to up-tune genes important for survival by escaping silencing,” said Zhangli Su, Ph.D., a postdoctoral researcher in the Department of Genetics and the first author of this study.
Short RNAs are like switches that, when turned on, decrease the expression of genes. Over a decade ago, Dutta’s lab discovered a novel family of short RNAs expressed in our cells that they named tRFs.
“In this paper, we report that the switches are themselves regulated. tRFs can be chemically changed by special cellular proteins so that they cannot decrease the expression of their target genes. Interestingly, these regulatory cellular proteins are increased in some cancers, and using bladder cancers as an example we showed that this decreases the activity of the tRFs, leading to the increased expression of target genes that make a cancer be more aggressive,” Dutta said.
Read more from UAB News about Dutta’s work.
The Heersink School of Medicine communications staff sat down with Dr. Anindya Dutta to gain insights about the research of this study, UAB, and the science community.
Zhangli Su, Ph.D.Q: What compelled you to pursue this research?
We were pursuing what genes are regulated by the switches (tRFs). A brilliant postdoctoral fellow in the lab, Dr. Zhangli Su, noticed a surprising anomaly in her results and followed up on it. She noticed that although certain tRFs were present in the cell, we could not pull them out to study them. Why? Following her own curiosity, she discovered that she could not fish them out because the tRFs are chemically modified, found the enzyme that does the modification, and then discovered that the modifying enzyme is increased in expression in bladder cancer.
Q: What was your most unexpected finding?
That the tRFs we have been studying for a decade are sometimes chemically changed by the cell to inactivate their switch activity.
Q: How do you feel your research will impact the science community?
The community will begin to look for other chemical changes not only on tRFs, but other families of short RNAs, to determine if this is a widespread mechanism of regulating short RNA activity.
Q: What is your research’s relevance to human disease?
The increased activity of the modifying enzyme (the protein that makes the chemical changes on the tRFs), helps a cancer to turn off the switches and thus increases the expression of cancer-causing genes. This immediately raises the possibility that chemicals (drugs) that either inhibit the modifying enzyme or reverse the modification (the chemical change on the tRFs) will help decrease the expression of cancer-causing genes, providing yet another target for developing cancer therapy.
Q: What made you come to UAB?
UAB is in an extremely exciting stage of growth. The University, including the Department of Genetics, is expanding its research and clinical enterprise by bringing in the best faculty from all over the world. There has been significant investment in genetics, genomics, and bioinformatics, that will begin to pay off by making new discoveries and finding better ways to serve our patients. When I looked at the full picture of what is going on here, I wanted to be a part of the action. I have been here for just over a year now and continue to be excited about the growth potential of the place.