When a gene is expressed, its DNA sequence is transcribed into a molecule known as RNA. Then the cell processes and edits that RNA before it is translated into protein. Many genes can be processed and edited in various ways. So while genes have traditionally been thought of as sequences that encode for one protein, the reality is that many genes can encode for more than one protein. RNA editing typically involves splicing out certain sequences, and RNA molecules can often be spliced in alternative ways. Now researchers have found that alternative RNA splicing may help certain mammals live much longer than other mammals. The findings have been reported in Nature Communications.
In this study, scientists compared various ways that RNA is edited in 26 species of mammals with maximum lifespans that range from only 2.2 years to 37 years. This effort analyzed RNA transcripts in six tissue types, such as the brain. The analysis focused more on gene splicing than gene activity, and indicated that splicing has a significant influence on the maximum lifespan of a mammal.
The investigators showed that splicing patterns that are related to lifespans can be common to many species, and are also linked to the maximum lifespan of a mammal.
"We've long known that gene expression likely contributes to lifespan controls, but our study shows that how those genes are edited through splicing offers a novel and parallel dimension to this process," noted co-corresponding study author Sika Zheng, a professor of biomedical sciences at the University of California, Riverside (UCR) School of Medicine, among other appointments. "It's like discovering a hidden layer of genetic control that shapes lifespan in ways we had not appreciated before."
The study also showed that there were two times as many splicing events linked to lifespan in the brain compared to other tissues.
"This likely reflects the brain's specialized functions and regulatory complexity, with many splicing factors expressed only in neural tissue," Zheng explained. "These findings identify the brain as a key site of lifespan regulation and suggest that longevity depends heavily on neural maintenance and adaptability. Brain-specific splicing may therefore be a promising target for promoting healthy aging and preventing neurodegenerative disease."
Splicing events that were associated with lifespan were found to be tightly regulated by proteins that bind to RNA, and were not a byproduct of the aging process.
This may indicate that species that live longer have molecular programming that encourages splicing events that boost longevity, and environmental influences may modify these processes, added Zheng. "Splicing broadens the way we think about longevity and how we might influence it."
Sources: University of California Riverside, Nature Communications
