AUF1 protects against aging by preventing telomere shortening
The AUF1 protein (AU-rich element RNA-binding protein 1) binds to the matrix RNAs of cytokines and other proteins containing the so-called adenosine/uridine-enriched elements (adenosine/uridine-rich element, ARE) in the non-coding 3’ region, and destroys them, thereby suppressing the synthesis of proteins that activate inflammatory reactions.
In addition, it is known that this protein prevents cell aging, but the mechanism of its geroprotective action is not fully understood.
Researchers from the University of New York, working under the leadership of Robert Schneider, when studying genetically modified mice deprived of the AUF1 protein, received additional data on the mechanism by which AUF1 slows down the aging process.
In addition to the weakening of inflammatory reactions, mice without this protein began to show signs of physiological aging in every cell of the body before the due date. Moreover, the reproductive capacity of animals decreased significantly with each subsequent generation. These symptoms reminded scientists of the manifestations associated with the absence of telomerase, an enzyme that restores the end sections of the DNA telomere that shorten with each cell division.
Analysis of telomerase activity showed that, compared with wild-type animals, mice without AUF1 protein were indeed characterized by reduced telomerase levels, as well as shorter telomeres. It also turned out that the AUF1 protein is able to bind to the promoter region of the telomerase gene and activate its transcription.
According to experts, the ability of the protein binding matrix RNA to interact with DNA is not particularly surprising, but its active role in transcription is quite unexpected. The discovery of this phenomenon will undoubtedly prompt many researchers to search for similar abilities in other RNA-binding proteins.
To date, it is unclear how AUF1 recognizes the telomerase gene promoter and binds to it, but Schneider and his colleagues have already identified two protein isoforms responsible for this. Apparently, they differ from the other two isoforms of AUF1, whose function is to degrade the informational RNA on which proinflammatory factors are synthesized.
Experts believe that further detailed study of the issue will shed light on many issues. For example, it explains why malignant neoplasms are characterized by increased expression of AUF1: apparently, tumor cells use it to activate telomerase transcription.
The article by Adam R. Pont et al. mRNA Decay Factor AUF1 Maintains Normal Aging, Telomere Maintenance, and Suppression of Senescence by Activation of Telomerase Transcription is published in the journal Molecular Cell.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: The Aging and Inflammation Link.
28.05.2012