Scientists have found that some sub-segments of RNA considered junk have a functional role in inhibiting the production of certain Messenger RNAs and appear to help cells cope with oxidative stress.
The fragments in question are introns, short sequences that transfer part of RNA, and RNA molecules help guide the assembly of amino acid chains during protein construction. Historically, these introns have been considered useless for cells because they have to be cut off before the trnar is done.
In a new study, Ohio State University researchers show that some introns attach to key parts of the molecule that convert genetic information into proteins, causing them to degrade – thus eliminating the production of proteins. In experiments exposed to cellular oxidative stress, an intron remained highly stable under those conditions, rather than decomposed, suggesting that some introns may be part of the cell evolutionary survival toolkit.
Years of unexpected observations have led scientists to study the functional role of what they call “fitrnas”, a brief of the free introns of TRNA: an incredible sequencing relationship with other RNA molecules, various methods used by cells to discard them, and overexpress certain, certain, certain, certain overexpression, but not all introns under stress conditions.
“No one expects the function of introns. But that doesn’t make sense to me because they don’t have any functions, but the cell thinks there should be six or more different ways to destroy them.” Ohio State University Molecular Genetics Professor Anita Hopper said.
“If cells are just garbage, why should cells prioritize them? We think there must be some functionality. Over the past five years, our team has designed some very wise experiments to prove this.”
The study today (February 11, 2025) Molecular cells.
Transfer RNA (TRNA) and Messenger RNA (mRNA) build proteins through complementarity, which means that the tRNA sequence pair is paired with complementary sequences on the mRNA molecule to ensure that the correct amino acids are added to the strands, because the protein is a protein that is built. .
Hopper’s team used yeast as a research model a few years ago to show that some relaxed intron sequences complement the mRNA sequence, suggesting that introns may have important significance for the translation of genetic code. There are 10 tRNA families containing introns, each of which is destroyed in a unique way. The focus of this study was on two of these families.
The researchers found that once released from the tRNA, these floating introns with complementary sequences bind to specific mRNAs, which causes the mRNA to scatter and therefore no protein production occurs. Experiments have confirmed a clear inverse relationship: deletion or induction of FITRNA overexpression leads to a corresponding increase or decrease in target mRNA.
Regina Nostramo, a postdoctoral researcher at Hopper’s Lab, said FITRNA functions appear to be similar to microRNA, smaller RNA (also once considered garbage), but there are significant differences. But there are significant differences.
MicroRNA interacts with proteins from the Argonaute family to degrade messenger RNA, “But because there is no Argonaute protein in this yeast, something else is happening, and Messenger RNA is still degrading. So, this is a similar mechanism, but The details of what happened are different,” Nostramo said.
Hopper notes that there is another difference: microRNAs are always attached to the same non-coding “seed” region of their target messenger RNA, but the released introns bind to the mRNA portion containing the indication of protein construction.
“So it’s not only a newly discovered small non-coding RNA, but it also runs in a novel way,” she said.
The ability to inhibit protein production shows that introns can give cells an advantage, the researchers say. Paolo Sinopoli, co-author of Paolo Sinopoli, a third-grade molecular genetics student in Hopper’s lab, identified at least 33 mRNAs targeted by a family of introns. Although they do not fall into one category, the affected proteins tend to be associated with cell division and reproduction.
“The problem we have is, ‘Why is the intron starting to exist?’” Sinopoli said. “From the trna, they are present in humans, mice, flies, yeasts. So, although they seem to be inefficient, they are present in all of these organisms, but the inefficient things in biology often don’t stick to them. ”
The abundance and stability of a fitna in cells undergoing oxidative stress provides a clue to their importance, that the team will continue to pursue by exposing the cells to heat stress, hunger and other challenging situations. .
“Perhaps the cells use these small introns as negative regulators of gene expression because they are not destroyed under certain conditions,” Hopper said. “Perhaps they have a small role in healthy cellular conditions,” he said. But under pressure, when some of them are stable, maybe that’s a very important role.”
This work was supported by the National Institutes of Health, the Burrowtoni Undergraduate Scholarship and the Ohio Undergraduate Research Fellowship.
Other co-authors from Ohio State are Alicia Bao (now at Thomas Jefferson University), Sara Metcalf and Lauren Peltier (now at the University of Toledo).
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