AUG 03, 2021 8:04 AM PDT

Aging Cells May Lose Control of Where an mRNA Sequence Starts

WRITTEN BY: Carmen Leitch

When a gene is active, it's transcribed from DNA to RNA, and a specific sequence in the genetic code acts like a signpost so the cellular machinery knows where it should start transcribing a gene. But researchers have found that sometimes there are other places where transcription might start, so-called cryptic start sites. Scientists have found evidence of this process occurring in yeast cells and a worm model, and have found that in mammalian cells that have aged, cryptic transcription occurs more often that in cells that aren't aging.

Image credit: Public domain pictures

Now reporting in Nature Aging, scientists have found evidence that a cellular process that regulates cryptic transcription and keeps it under control begins to break down as it gets older. It may be possible to prevent cryptic transcription in an effort to extend longevity.

“In previous work, we showed that cryptic transcription in yeasts and worms is not only a marker of aging but also a cause,” said corresponding study author Dr. Weiwei Dang, an assistant professor of molecular and human genetics at Baylor College of Medicine. “Reducing the amount of this aberrant transcription in these organisms prolonged their lifespan.”

The cell's machinery 'reads' DNA sequences in sets of three nucleotide bases, called codons. Transcription begins at a codon that has an DNA sequence of ATG, which is where the cell's RNA polymerase enzyme starts making the messenger RNA (mRNA) for a protein, and may be upstream of the actual protein sequence; this mRNA is usually processed by the cell before being translated into a protein. The ATG codon also codes for an amino acid called methionine, so it might be found in other places in a gene's sequence.

As Dang explained, “promoter look-alike sequences do exist in other locations, 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 increased with age in mammals and potential mechanisms involved in this phenomenon.”

In this study, the researchers detected cryptic transcription events to get an idea of how often it happens in a variety of cell types. They noticed that older cells had higher levels of cryptic transcription than younger cells. Further work with more aging cells confirmed that finding.

“Altogether, our findings indicate that elevated cryptic transcription is a hallmark of mammalian aging,” Dang said.

While younger cells can stop cryptic transcription from happening, these preventive mechanisms become dysfunctional as mammalian cells age. One of those mechanisms involves chromatin, which keeps the genome organized and packed, and can physically prevent or allow transcriptional machinery to access certain parts of the genome.

“It is still not clear how elevated cryptic transcription contributes to aging, but the evidence is accumulating that it is detrimental to mammals as it is for yeast and worms,” Dang said. “Future studies may result in ways of reduce the pro-aging effects of cryptic transcription.”

Sources: AAAS/Eurekalert! via Baylor College of Medicine, Nature Aging

 

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
OCT 11, 2021
Microbiology
Small RNAs are Influential in Bacteria, Including Pathogens Like V. Cholerae
OCT 11, 2021
Small RNAs are Influential in Bacteria, Including Pathogens Like V. Cholerae
Like other organisms, bacteria have to take nutrients up from the environment and use them in various metabolic processe ...
OCT 12, 2021
Clinical & Molecular DX
Tiny Fragments of RNA in the Blood Signal Dementia Risk
OCT 12, 2021
Tiny Fragments of RNA in the Blood Signal Dementia Risk
Scientists have discovered a novel biomarker in the blood that acts as an early warning sign for dementia: microRNA. The ...
OCT 17, 2021
Genetics & Genomics
Genes That Cause Disease Seem to Prevent Beneficial Adaptations
OCT 17, 2021
Genes That Cause Disease Seem to Prevent Beneficial Adaptations
A new study has used computational tools to investigate evolution in the human genome that's occurred over the past 50,0 ...
NOV 02, 2021
Cell & Molecular Biology
Amino Acid Supplements May Prevent Neuronal Death & Dementia
NOV 02, 2021
Amino Acid Supplements May Prevent Neuronal Death & Dementia
Dementia is an umbrella term for several age-related disorders that can cause cognitive problems such as dysfunction in ...
NOV 08, 2021
Genetics & Genomics
Revealing Gene Expression Networks in Human Embryonic Stem Cells
NOV 08, 2021
Revealing Gene Expression Networks in Human Embryonic Stem Cells
Advances in genetic and computational tools have enabled researchers to study complex networks of gene expression in ind ...
NOV 09, 2021
Plants & Animals
It Seems a Single Molecule Can Govern Ant Behavior
NOV 09, 2021
It Seems a Single Molecule Can Govern Ant Behavior
Some people change careers, and it seems that the Harpegnathos saltator ant can do the same; worker ants can switch to q ...
Loading Comments...