DNA, protein, and RNA are tied together by transcription factors in this process.
In the world of gene regulation, transcription factors serve as the multi-purpose tools, boasting regions that can bind both DNA and proteins. These handy proteins help regulate gene expression, flipping genes on or off, or adjusting their activity level, often working in tandem with the proteins they bind. They station themselves and their partners at DNA binding sites within genetic regulatory sequences, bringing together the essential components required for gene expression to take place.
A recent study by MIT's very own Professor of Biology and Whitehead Institute for Biomedical Research member Richard Young and colleagues sheds new light on the functionality of transcription factors. As published in the prestigious journal Molecular Cell on July 3, Young, along with his Whitehead Institute postdocs Ozgur Oksuz and Jonathan Henninger, disclosed that these factors can also bind RNA, serving as a potential game-changer in our understanding of gene regulation.
The researchers discovered that RNA binding keeps transcription factors near their DNA binding sites for an extended period, enabling fine-tuning of gene expression. This paradigm shift may uncover intricacies in gene regulation and could pave the way for new targets in RNA-based therapeutics.
Speaking of the breakthrough, Young likened the scenario to discovering a new use for a Swiss Army knife. "It's like the odd, small piece at the back of the knife is a screwdriver. It's been there all along, and now that we see it, it's clear how many more uses there are for the knife than we realized."
So, how did researchers miss this RNA binding trick up until now? A few studies had hinted at a few transcription factors' ability to bind RNA, but they were dismissed as rare exceptions. Young, Oksuz, Henninger, and their team found that RNA binding is, in fact, a common characteristic present in at least half of transcription factors.
The researchers, in their quest to delve deeper, found a clue in the human immunodeficiency virus (HIV). HIV generates a transcription factor-like protein called Tat, which enhances the transcription of the virus’s RNA genome by binding to the virus's RNA and recruiting cellular machinery. Tat lacks a structured RNA binding site; instead, it binds RNA from an arginine-rich motif (ARM) that is unstructured but has a high affinity for RNA.
Wondering if Tat might be more similar to human transcription factors than previously thought, the researchers combed through the list of transcription factors, searching for ARMs instead of looking for structured RNA binding domains. They found many transcription factors with ARMs, highlighting that our understanding of transcription factor function had been somewhat incomplete.
The scientists then tested whether RNA binding influenced the transcription factors' functions, and their findings were illuminating. When individual transcription factors' ARMs were mutated, rendering them incapable of binding RNA, their ability to locate, remain at their target sites, and regulate genes waned.
The research team further discovered that the ARM of a crucial transcription factor in embryonic development held the key to developmental defects in zebra fish, underscoring the importance of RNA binding in transcription factor function. They also uncovered a number of genetic mutations known to contribute to cancer and heritable diseases occurring in the RNA binding regions of transcription factors.
All these findings underscore the role of RNA binding in transcription factor regulation and provide potential therapeutic opportunities. As Henninger explains, existing RNA-based technologies could be employed to target RNA molecules, thereby potentially increasing or decreasing gene expression in disease settings. Exciting times lie ahead for researchers and therapists alike, as we dive deeper into the intricate mechanisms governing gene regulation.
- The study by Richard Young and his colleagues, published in Molecular Cell, revealed that transcription factors can bind RNA, challenging the traditional understanding of gene regulation in health-and-wellness and science.
- Interestingly, the researchers found that RNA binding is a common characteristic among at least half of transcription factors, suggesting that previous studies may have underestimated the function of these factors in biology.
- The research team's findings imply that RNA-based therapeutics might be developed to target RNA molecules and adjust gene expression in conditions related to mental health, cancer, and other heritable diseases, opening new avenues for research in press and health-and-wellness.
