RNA that doesn't age

Certain RNA molecules in the nerve cells in the brain last a life time without being renewed. Neuroscientists from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have now demonstrated that this is the case together with researchers from Germany, Austria and the USA. RNAs are generally short-lived molecules that are constantly reconstructed to adjust to environmental conditions. With their findings that have now been published in the journal Science, the research group hopes to decipher the complex aging process of the brain and gain a better understanding of related degenerative diseases.

Most cells in the human body are regularly renewed, thereby retaining their vitality.

However, there are exceptions: the heart, the pancreas and the brain consist of cells that do not renew throughout the whole lifespan, and yet still have to remain in full working order.

"Aging neurons are an important risk factor for neurodegenerative illnesses such as Alzheimer's," says Prof.

Dr. Tomohisa Toda, Professor of Neural Epigenomics at FAU and at the Max Planck Center for Physics and Medicine in Erlangen.

"A basic understanding of the aging process and which key components are involved in maintaining cell function is crucial for effective treatment concepts:"

In a joint study conducted together with neuroscientists from Dresden, La Jolla (USA) and Klosterneuburg (Austria), the working group led by Toda has now identified a key component of brain aging: the researchers were able to demonstrate for the first time that certain types of ribonucleic acid (RNA) that protect genetic material exist just as long as the neurons themselves.

"This is surprising, as unlike DNA, which as a rule never changes, most RNA molecules are extremely short-lived and are constantly being exchanged," Toda explains.

In order to determine the life span of the RNA molecules, the Toda group worked together with the team from Prof.

Dr. Martin Hetzer, a cell biologist at the Institute of Science and Technology Austria (ISTA). "We succeeded in marking the RNAs with fluorescent molecules and tracking their lifespan in mice brain cells," explains Tomohisa Toda, who has unique expertise in epigenetics and neurobiology and who was awarded an ERC Consolidator Grant for his research in 2023.

"We were even able to identify the marked long-lived RNAs in two year old animals, and not just in their neurons, but also in somatic adult neural stem cells in the brain."

In addition, the researchers discovered that the long-lived RNAs, that they referred to as LL-RNA for short, tend to be located in the cells' nuclei, closely connected to chromatin, a complex of DNA and proteins that forms chromosomes.

This indicates that LL-RNA play a key role in regulating chromatin.

In order to confirm this hypothesis, the team reduced the concentration of LL-RNA in an in-vitro experiment with adult neural stem cell models, with the result that the integrity of the chromatin was strongly impaired.

Read more at Science Daily

RNA for the first time recovered from an extinct species

A new study shows the isolation and sequencing of more than a century-old RNA molecules from a Tasmanian tiger specimen preserved at room temperature in a museum collection. This resulted in the reconstruction of skin and skeletal muscle transcriptomes from an extinct species for the first time. The researchers note that their findings have relevant implications for international efforts to resurrect extinct species, including both the Tasmanian tiger and the woolly mammoth, as well as for studying pandemic RNA viruses.

The Tasmanian tiger, also known as the thylacine, was a remarkable apex carnivorous marsupial that was once distributed all across the Australian continent and the island of Tasmania. This extraordinary species found its final demise after European colonization, when it was declared as an agricultural pest and a bounty of £1 per each full-grown animal killed was set by 1888. The last known living Tasmanian tiger died in captivity in 1936 at the Beaumaris Zoo in Hobart, Tasmania.

Recent efforts in de-extinction have focused on the Tasmanian tiger, as its natural habitat in Tasmania is still mostly preserved, and its reintroduction could help recovering past ecosystem equilibriums lost after its final disappearance. However, reconstructing a functional living Tasmanian tiger not only requires a comprehensive knowledge of its genome (DNA) but also of tissue-specific gene expression dynamics and how gene regulation worked, which are only attainable by studying its transcriptome (RNA).

"Resurrecting the Tasmanian tiger or the woolly mammoth is not a trivial task, and will require a deep knowledge of both the genome and transcriptome regulation of such renowned species, something that only now is starting to be revealed," says Emilio Mármol, the lead author of a study recently published in the Genome Research journal by researchers at SciLifeLab in collaboration with the Centre for Palaeogenetics, a joint venture between the Swedish Museum of Natural History and Stockholm University.

RNA molecules recovered from the Tasmanian tiger

The researchers behind this study have sequenced, for the first time, the transcriptome of the skin and skeletal muscle tissues from a 130-year-old desiccated Tasmanian tiger specimen preserved at room temperature in the Swedish Museum of Natural History in Stockholm. This led to the identification of tissue-specific gene expression signatures that resemble those from living extant marsupial and placental mammals.

The recovered transcriptomes were of such good quality that it was possible to identify muscle- and skin-specific protein coding RNAs, and led to the annotation of missing ribosomal RNA and microRNA genes, the later following MirGeneDB recommendations.

"This is the first time that we have had a glimpse into the existence of thylacine-specific regulatory genes, such as microRNAs, that got extinct more than one century ago," says Marc R. Friedländer, Associate Professor at the Department of Molecular Biosciences, The Wenner-Gren Institute at Stockholm University and SciLifeLab.

This pioneering study opens up new exciting opportunities and implications for exploring the vast collections of specimens and tissues stored at museums across the globe, where RNA molecules might await to be uncovered and sequenced.

"In the future, we may be able to recover RNA not only from extinct animals, but also RNA virus genomes such as SARS-CoV2 and their evolutionary precursors from the skins of bats and other host organisms held in museum collections," says Love Dalén, Professor of evolutionary genomics at Stockholm University and the Centre for Palaeogenetics.

Read more at Science Daily