Nobel Prize in Physiology or Medication Awarded for Discovery of MicroRNA Gene Regulation

Nobel Prize in Physiology or Medication Awarded for Discovery of MicroRNA Gene Regulation

By Tanya Lewis

Each cell in our physique comprises the identical set of genetic directions, or DNA. But solely a few of these genes are expressed in every cell, resulting in the manufacturing of proteins that carry out the cell’s distinctive features. The 2024 Nobel Prize in Physiology or Medication was awarded on Monday to U.S. scientists Victor Ambros and Gary Ruvkun for the invention of microRNA, a molecule that performs this vital regulatory course of.

The invention opened up a brand new discipline in gene regulation, explaining how solely a few of the many genetic directions in DNA lead to useful proteins in several cells. The analysis was initially carried out within the tiny roundworm Caenorhabditis elegans, however the mechanism has since been discovered within the genes of people and most different animals.

Ambros carried out his a part of the work at Harvard College, and he’s presently a professor of pure sciences on the College of Massachusetts Chan Medical College. Ruvkun carried out his analysis concurrently at Massachusetts Normal Hospital and Harvard Medical College, the place he’s now a professor of genetics.

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“The seminal discovery of microRNA has introduced a new and unexpected mechanism of gene regulation,” mentioned Olle Kämpe, vice chair of the Nobel Committee for Physiology or Medication 2024, whereas describing the analysis throughout a press convention in Stockholm on Monday.

In cells, genes are transcribed into messenger RNAs (mRNAs), that are then translated into proteins. Proteins carry out the numerous very important features inside any cell, whether or not that cell is in nerve tissue, muscle or the immune system—or anyplace else. Issues with gene perform can result in situations resembling most cancers, diabetes and autoimmune illness.

As early because the Sixties scientists had found that proteins known as transcription components may bind to genes and management what elements of these genes obtained transcribed into mRNA. This mechanism was considered the first method genes have been regulated. However gene regulation turned out to be extra sophisticated.

Within the Nineteen Eighties Ambros and Ruvkun have been working collectively as postdoctoral fellows on the laboratory of Robert Horvitz, who shared the 2002 Nobel Prize in Physiology or Medication for describing the genetic regulation of cell dying in C. elegans. Researchers working with these organisms had beforehand found two “mutant” genetic types of the roundworm that developed otherwise. One in every of them, often known as lin-4, resulted in a bigger worm, whereas the opposite, lin-14, led to a smaller one. Ambros confirmed that the lin-4 gene was negatively regulating the lin-14 gene, however it wasn’t clear the way it did so.

Later, at Harvard, Ambros labored to “clone” or make copies of the lin-4 gene—however this resulted in a really tiny RNA molecule that was too small to provide a protein. On the similar time, Ruvkun, then at Mass Normal and Harvard, was finding out lin-14. He discovered that lin-4 was not blocking the manufacturing of lin-14 on the mRNA stage however was moderately impeding its translation into protein at some later stage. Ruvkun and Ambros determined to match their findings and located that a part of the sequence of the lin-4 mRNA matched that of the lin-14 mRNA’s finish area, which isn’t concerned in encoding a protein. They found that the binding of this lin-4 mRNA to lin-14 mRNA prevented the latter from producing a protein. This represented a newly discovered mechanism of gene regulation that was orchestrated by tiny molecules known as microRNA.

At first, the researchers thought this mechanism is likely to be distinctive to C. elegans. However in 2000 Ruvkun recognized a second microRNA known as let-7 that was current in people and all through the animal kingdom. Scientists now know that people have greater than 1,000 totally different microRNA genes and that almost all of genes are regulated by microRNA.

The disruption of those microRNA networks is believed to play a job in how cancers develop, pointing towards potential remedies.

Ambros and Ruvkun “were looking at two worms that looked a bit funny and decided to understand why, and then they discovered an entirely new mechanism for gene regulation,” Kämpe mentioned on the press convention. “I think that’s beautiful.”

Editor’s Word (10/7/24): This story is being up to date.