New Insights into Disease-Fighting “Transcriptional Noise”

New Insights into Disease-Fighting “Transcriptional Noise”

In the process of gene expression, a gene’s DNA instructions for making proteins are transcribed, or converted, into RNA, which then acts a template for protein synthesis. Large and seemingly random fluctuations occur in the transcription of DNA into RNA—fluctuations referred to as “transcriptional noise.”

The actual purpose of transcriptional noise remains unclear—and even less is known about how it’s regulated. For years, transcription noise was thought to be caused by genes switching back and forth between their “on” and “off” states. Now, in a study published August 20 in Science, researchers at Einstein and other institutions describe a previously unknown regulator of transcriptional noise.

Involvement of the Einstein researchers—Robert H. Singer, Ph.D., and Robert Coleman, Ph.D.,—came after Leor Weinberger, Ph.D., at the University of California, San Francisco identified small molecules that boosted transcriptional noise at many different genes in stem cells. Dr. Weinberger and colleagues asked Drs. Singer and Coleman at the Gruss Lipper Biophotonics Center to determine how the molecules induced dynamic changes in transcriptional noise at a key gene involved in fighting cancer.

Combining state-of-art single-cell sequencing at UCSF with single-molecule imaging methods at Einstein, the researchers found that the small molecules increased transcriptional noise at the cancer-fighting gene via a cellular mechanism they identified and dubbed DiThR (short for Discordant Transcription through Repair). The findings may allow scientists to devise strategies for engineering stem cells for therapeutic purposes.

Dr. Singer is professor and co-chair of anatomy and structural biology, as well as co-director of the Gruss Lipper Biophotonics Center and of the Integrated Imaging Program at Einstein. He is also professor in the Dominick P. Purpura Department of Neuroscience and of cell biology and the Harold and Muriel Block Chair in Anatomy & Structural Biology at Einstein. Dr. Coleman is an associate professor of anatomy and structural biology at Einstein.