Cryptic transcription, a new phenomenon in mammalian rods

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HOUSTON – While the visible signs of aging are usually unmistakable, figuring out what triggers them has been quite a challenge. Researchers at Baylor College of Medicine and collaborating institutions have found that a cellular phenomenon called cryptic transcription, which had previously been described and linked to the aging of yeasts and worms, is elevated in aging mammalian stem cells.

The team reports in the newspaper Natural aging this cryptic transcription occurs because a cellular mechanism that controls it breaks down as cells age. The results suggest that strategies that control cryptic transcription may have effects on longevity.

“In previous work, we have shown that cryptic transcription in yeasts and worms is not only a marker of aging, but also a cause,” said corresponding author Dr Weiwei Dang, assistant professor of Molecular and Human Genetics and the Huffington Center on Aging at Baylor. . “Reducing the amount of this aberrant transcription in these organisms prolonged their lifespan.”

Cryptic transcription is a phenomenon that interferes with normal cellular processes. Normal gene transcription is a first step in the production of proteins. It starts at a specific place in DNA called a promoter. This is where the gene encoding the protein begins to be transcribed into RNA, which is ultimately translated into protein. Gene transcription is a well-regulated cellular process, but as cells age they lose their ability to control it.

“Promoters have a specific DNA sequence that identifies the starting point of the transcription process which is usually located before the actual protein coding sequence,” Dang explained.

“But similar promoter sequences exist in other places, including along the actual protein coding sequence, and they could start transcription and generate shorter transcripts, called cryptic transcripts. Here, we investigated whether cryptic transcription increases with age in mammals and the potential mechanisms involved in this phenomenon.

The team worked with mammalian stem cells, which have been shown to play an important role in aging. They adapted a method to detect cryptic transcription in order to determine the level of this transcription in mice and human stem cells and cells in culture.

Compared to young stem cells, the older ones exhibited increased cryptic transcription. They also looked at other aging cells and found that in the majority of cells spanning a range of tissues, cryptic transcription was also elevated with age.

“Overall, our results indicate that high cryptic transcription is a hallmark of aging mammals,” Dang said.

Young cells have mechanisms in place to prevent cryptic transcription. In aged mammalian cells, researchers have found that one of these mechanisms, which involves limiting access to chromatin, the material that makes up chromosomes, fails, making it easier to produce cryptic transcripts.

“It is still not clear how high cryptic transcription contributes to aging, but evidence is mounting that it is detrimental to mammals as it is to yeasts and worms,” Dang said. “Future studies may lead to ways to reduce the pro-aging effects of cryptic transcription. “

Other contributors to this work include Brenna S. McCauley, Luyang Sun, Ruofan Yu, Minjung Lee, Haiying Liu, Dena S. Leeman, Yun Huang, and Ashley E. Webb.

The authors are associated with one or more of the following institutions: Baylor College of Medicine, Texas A&M University, University of Texas MD Anderson Cancer Center, Stanford University, Genentech, and Brown University.

For more information, visit the BCM website; for previous articles on Baylor’s medical research, click here.


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