Tag Archives: RNA

RNA Strands with Near-Self-Replication Potential: The Key to Understanding the Origin of Life

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Artist's depiction of QT45 RNA molecule

Artist’s depiction of QT45 superimposed on a microscopy image of a frozen environment conducive to RNA replication (based on AlphaFold3 predictions)

Microscope images by Elfie Chan and James Atwater

According to the RNA World Hypothesis, life initiated with RNA molecules that evolved to replicate themselves. Recent discoveries reveal an RNA molecule capable of this self-replication, executing essential processes, though not simultaneously.

“It’s been a long quest to reach a point where we confidently state RNA can replicate itself under the right conditions, showcasing its potential,” says Philip Holliger at the MRC Molecular Biology Laboratory, Cambridge, UK.

In living organisms, proteins are pivotal, catalyzing chemical reactions while their synthesis instructions are encoded in double-stranded DNA. RNA, existing typically as a single strand, serves as a chemical analog of DNA.

While RNA is not as reliable for information storage due to its instability, it exhibits a unique capability: folding into protein-like enzymes that catalyze chemical reactions. This dual function of RNA as both storage and catalyst led to the hypothesis in the 1960s that the genesis of life may have hinged on self-catalyzing RNA molecules.

However, identifying such self-replicating molecules has proved exceptionally challenging. It was previously assumed that self-replicating RNA would be relatively large and complex, yet large RNAs are cumbersome to spread and duplicate.

Furthermore, while shorter RNA molecules have been known to form spontaneously under suitable conditions, the likelihood of larger molecules doing the same remains low.

“This insight led us to reconsider; perhaps something simpler and smaller could efficiently complete this process,” Holliger explains. “That search yielded QT45.”

RNA comprises nucleotide building blocks. The research team initiated the process by generating 1 trillion random sequences, each 20, 30, or 40 nucleotides long. They selected three capable of binding nucleotides and combined them for several rounds of evolution, introducing random mutations to enhance performance.

The resultant molecule, QT45, is composed of just 45 nucleotides. In alkaline, near-freezing water, single-stranded RNA can serve as a template to join short strands of two or three nucleotides, creating complementary strands, including those that mirror itself. “Although the process is currently slow with low yields, this is expected,” notes Holliger.

QT45 can also replicate itself using its complementary strands. “This is the first instance of RNA that can generate itself and its coding strand, representing the two core reactions of self-replication,” states Holliger. However, the team has yet to achieve both reactions occurring within the same container. Future efforts will focus on further evolving the molecule and experimenting with conditions like freeze-thaw cycles to see if simultaneous reactions are possible.

“The most fascinating aspect is that once the system begins self-replication, it also starts self-optimization,” Holliger adds, as the error-prone process generates various variants, some potentially more effective at replication.

“The findings from the Holliger lab represent a vital step toward fully self-replicating RNA.” asserts Sabine Muller from the University of Greifswald, Germany.

“A key takeaway from this discovery is the identification of intermediate-sized RNA oligomers capable of self-synthesizing,” remarks Zachary Adam at the University of Wisconsin-Madison.

The vast number of possible 45-nucleotide-long RNA sequences is “inconceivably large,” Adam notes, making the team’s discovery of QT45 from an initial batch of 1 trillion sequences mind-boggling.

In early Earth’s environment, a molecule akin to QT45 might have successfully replicated itself amidst conditions similar to those in modern-day Iceland, combining ice with hydrothermal activity that creates freeze-thaw cycles and pH gradients. Holliger believes compartmentalization is essential to segregate key components, with numerous possibilities for this occurrence, from pockets of meltwater in ice to cellular vesicles spontaneously formed from fatty acids.

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  • Origin of Life

Source: www.newscientist.com

RNA Molecules Discovered in 39,000-Year-Old Woolly Mammoth Tissue

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Researchers have successfully extracted and sequenced ancient RNA from the tissues of 10 woolly mammoths preserved in permafrost. One of these specimens is estimated to be 39,000 years old, making it the oldest ancient RNA sequence recorded to date.

Marmol Sanchez et al. Ancient RNA sequences identified in late Pleistocene woolly mammoth tissue. Image credit: Marmol Sanchez et al., doi: 10.1016/j.cell.2025.10.025.

Investigating prehistoric genes and their activation is crucial for understanding the biology and evolution of extinct species.

For years, scientists have been piecing together the mammoth genome and their evolutionary history through DNA analysis.

However, RNA, which indicates active genes, has remained elusive until now.

“With RNA, we can provide direct evidence of which genes are ‘turned on’ and gain insights into the final moments of mammoths that lived during the last Ice Age,” stated Dr. Emilio Marmol, a researcher at the Globe Institute.

“This kind of information cannot be obtained from DNA alone.”

In this study, Dr. Marmol and colleagues analyzed permafrost-preserved tissue from 10 late Pleistocene woolly mammoths discovered in northeastern Siberia, spanning from the central Indigirka region to the Oyogos Yar coast and the New Siberian Islands.

“We accessed exceptionally well-preserved mammoth tissue excavated from the Siberian permafrost, expecting it to contain RNA molecules that had remained frozen over millennia,” Marmol mentioned.

“We have pushed the limits of DNA recovery for over a million years,” said Professor Rav Dalen from Stockholm University and the Center for Paleogenetics.

“Now we aimed to determine if RNA sequencing could go further back than prior research.”

Researchers successfully identified tissue-specific gene expression patterns in the muscular remains of Yuka, a 39,000-year-old juvenile mammoth.

There are over 20,000 protein-coding genes in the mammoth genome, but not all are actively expressed.

The detected RNA molecules relate to proteins crucial for muscle contraction and metabolic regulation under stress.

Researchers also discovered several RNA molecules that regulate gene activity in mammoth muscle samples.

“We found non-protein-coding RNAs, such as microRNAs, which were among our most intriguing discoveries,” Dr. Mark Friedlander from Stockholm University’s Wenner-Gren Institute remarked.

“The muscle-specific microRNAs identified in mammoth tissue provide concrete evidence of gene regulation occurring in real-time in ancient eras. This is a groundbreaking achievement.”

The identified microRNAs also enabled the authors to confirm their findings originated from mammoths.

“We found a rare mutation in a specific microRNA, providing evidence that it is of mammoth origin,” noted Dr. Bastian Flom from the Norwegian Arctic University Museum.

“We also uncovered novel genes solely based on RNA evidence, a feat not attempted before at such ancient sites.”

“RNA molecules can endure for much longer than previously assumed.”

“Our findings demonstrate that RNA can survive much longer than previously thought,” Professor Dalen added.

“This allows us to not only explore which genes are ‘turned on’ in various extinct creatures but also to sequence RNA viruses like influenza and coronaviruses that are preserved in Ice Age remains.”

These findings were published in the Journal of Cell on November 14, 2025.

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Emilio Marmol-Sanchez et al. Ancient RNA expression profiles from extinct woolly mammoths. Cell published online on November 14, 2025. doi: 10.1016/j.cell.2025.10.025

Source: www.sci.news

RNA from Ancient Mammoths Offers Glimpse into Their Life 39,000 Years Ago

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Researchers published a study in the journal Cell on Friday. Until recently, it was believed that RNA could not survive for extended periods.

“Textbooks indicate that RNA is highly unstable and generally degrades within minutes of exiting a living cell,” remarked Marc Friedlaender, a computational biologist at Stockholm University and one of the study authors. “It’s truly remarkable that we discovered RNA dating back 40,000 years. No one thought this was feasible.”

This research may open up new avenues into historical understanding. Erez Eiden, a professor of biochemistry and molecular biology at the University of Texas Medical Branch, who was not involved in the study, noted that scientists will continue to refine the techniques used to analyze ancient RNA, similar to how they have done for years with ancient DNA.

Incorporating RNA analysis into the study of ancient genetics could fundamentally alter our perception of the biological history of the Earth, Eiden stated.

“We will be able to construct a more comprehensive and quantitative narrative of life’s history on our planet,” he added. “Suddenly, the Rosetta Stone appeared.…This is like an ancient hieroglyph of life.”

The discovery of RNA was facilitated by the find of Yuka in 2010, when members of the Yukagir community unearthed a mammoth in melting permafrost near the Arctic Ocean. Yuka was found resting on a cliff, partially mummified, and encased in a mat of strawberry blonde hair and flesh that remained pink until her discovery.

Paleontologists believe Yuka was pursued to death. Some evidence points to the creature being chased by a cave lion or possibly killed by modern humans. There are indications supporting both theories, with each species potentially playing a role in the extinction of this ancient animal.

In a world populated by cave lions, this creature experienced significant stress prior to its death.

Indeed, recent RNA analyses indicate that the profiled RNA displayed signs of physiological stress. The researchers utilized samples taken from the animal’s slow-twitch muscle fibers.

“We discovered that stress genes were activated,” Friedlander stated.

Laboratory work in an ultra-clean environment at the Paleogenetics Center in Stockholm where ancient RNA was extracted.
Provided by: Jens Olof Razin

Mammoths are not the only ancient species to have had their RNA analyzed. In 2019, researchers examined the RNA of 14,300-year-old wolf or dog pups.

RNA is synthesized from its DNA template through a process known as transcription. During transcription, certain genes are activated while others remain dormant.

This process is dynamic, and the genes expressed can fluctuate from day to night, according to Marmol Sanchez.

The researchers also identified a novel form of microRNA (a type of RNA governing gene expression) in mammoths that is unknown in modern elephants.

The RNA technology being developed may assist efforts to revive the woolly mammoth, as noted by Eiden, who is a member of the scientific advisory board for Colossal Biosciences, the company aiming to “resurrect” the woolly mammoth.

Professor Friedlander remarked that further research could also shed light on how some ancient viruses, which lack DNA, evolved over time.

“To understand the history of RNA viruses like SARS-CoV-2, we must detect these RNA molecules in historical and ancient samples to comprehend their evolution,” Friedlander explained.

Viruses such as Ebola, HIV, and influenza possess RNA genomes.

More research is required. In this study, the scientists investigated 10 mammoths but only obtained reliable RNA signals from three, including Yuka, the best-preserved specimen.

Since 2010, Yuka has been thought to be a female mammoth, but RNA and DNA analyses have revealed that she is, in fact, male.

Eiden highlighted that the RNA study underscores how little is understood about death and the varying rates of molecular breakdown after an organism’s demise.

“Our theories about what occurs to the physical matter of an organism post-mortem are still inadequate,” Eiden said. “What information is retained, and how legible can it remain over time? These are some intriguing questions.”

Source: www.nbcnews.com

Earliest RNA Sample Discovered from a Woolly Mammoth

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The skin and muscles of Yuka’s left front leg are remarkably intact.

love darren

The oldest known RNA has been obtained from a woolly mammoth preserved in Siberian permafrost for close to 40,000 years.

This specimen, named Yuka and found in 2010, is regarded as the best-preserved woolly mammoth (Mammuthus primigenius) identified to date. Initially believed to be a young female that perished between the ages of 6 and 8—likely due to an attack by a cave lion.

Researchers have successfully extracted DNA from various woolly mammoths, including some over a million years old. Advances in genome reconstruction have sparked hopes of potentially reviving this species through genetic engineering.

DNA carries the genetic blueprint for protein production in animals. When a specific gene is activated, the code is transcribed into another molecule known as RNA, which is far less stable than DNA and typically breaks down within hours after death.

The oldest RNA previously retrieved was from a wolf preserved in Siberian permafrost over 14,000 years ago. Recently, love darren from Stockholm University has extracted nearly three times the RNA amount from Yuka’s leg than had been recorded before.

The research team employed techniques similar to those used to extract RNA from contemporary samples, fine-tuning them to target smaller and older molecules.

“Yuka is exceptionally well preserved,” remarks Darren. “The specimen likely experienced deep freezing and prolonged burial in permafrost, evidenced by the preservation of both muscle tissue and wool-like fur. This significantly boosts the chance of RNA preservation.”

However, Yuka’s temporary thawing during transport from northeastern Siberia to Yakutsk posed a challenge. “We assumed that any truly ancient RNA still present in the sample would have degraded into smaller fragments,” says Darren.

The team exercised extreme caution to prevent sample deterioration and avoid contamination. “We utilized liquid nitrogen for grinding, along with sterile materials, filtered air, protective clothing, and controlled lab conditions to eliminate modern contamination in sequencing data,” he explains.

RNA sequencing reveals which genes were active at the time of the animal’s death. In the RNA extracted from Yuka’s muscle and skin, the researchers identified signs of gene activity associated with muscle metabolism and cellular stress, aligning with the hypothesis of Yuka’s death resulting from a cave lion’s attack.

A surprising finding was that a combination of DNA and RNA analysis led the research team to conclude that Yuka was actually male. “I’ve anticipated something like this for a long time,” shares Darren. “Even though Yuka is remarkably preserved for being 40,000 years old, it’s not entirely intact, making it difficult to determine an organism’s morphological sex.”

Researchers also probed for RNA viruses such as influenza and coronaviruses but found no significant results. “Yet I believe we will see future studies on Ice Age RNA viruses,” Darren mentions. “For instance, we possess some Pleistocene bird carcasses that would be intriguing to investigate concerning avian influenza.”

Darren, a scientific advisor to Colossal Biosciences, the company claiming to have revived the dire wolf earlier this year, stated that the RNA sequences retrieved in this study do not directly contribute to the revival of the mammoth. However, the study may offer valuable insights into genes responsible for certain traits. “In the future, mammoth RNA profiles might uncover how specific traits, such as wool, were genetically regulated in these animals.”

Merlin Crossley, a researcher at the University of New South Wales in Sydney, noted that while acquiring such ancient RNA is an impressive feat, it doesn’t reveal much about mammoth ecology. “It’s akin to maneuvering a light airplane under the Sydney Harbor Bridge,” he explained. “It’s a remarkable technical accomplishment, but we gain little insight from it.”

Crossley believes that while older RNA samples may be unearthed in the future, the limits of RNA’s longevity are close at hand. Given the rarity of specimens like Yuka’s, he concludes that it’s unlikely that additional mammoths will yield significant information.

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Source: www.newscientist.com

Blood tests indicates RNA may pose a risk of pre-lammosis

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Pre-Lamp Disease is a potentially serious complication of pregnancy

Half Point Image/Getty Image

Pre-lamp syndrome can lead to many pregnancy complications, including death, but can be difficult to detect in the early stages of pregnancy. New blood tests can help doctors identify people at risk of developing a condition before symptoms begin.

“We can narrow it down to four really high-risk pregnancies. That’s a big step.” Maneesh Jain at Mirvie, a California-based health startup.

Pre-salping syndrome is a type of hypertensive disorder (HDP) during pregnancy, which occurs when scientists are not sure exactly – occurs during placenta development. This can lead to high blood pressure and lead to cardiovascular disease, organ damage, seizures and even death. It can also cause harm to the developing fetus.

However, catching pre-lammosis and other HDP is difficult. This is because symptoms usually do not appear for at least 20 weeks after pregnancy. Sometimes, no signs are detected until work. It is difficult to monitor placenta development. This is because taking tissue samples from organs is very invasive.

New blood tests are relatively non-invasive and use RNA markers to predict whether someone may develop HDP. Specifically, this test focuses on specific genes PAPPA2 and CD163its overexpression was previously linked to HDP. The researchers wanted to see if they could detect this overexpression of blood samples.

Their validation studies of over 9,000 pregnant people suggest that they can: Jain says that tests can be determined with accuracy of over 99% and above with accuracy of over 99%, whether people without existing risk factors overexpress the gene and therefore are at higher risk of pre-ec syndrome or another HDP. Almost a quarter of participants without existing HDP risk factors overexpressed the gene.

People with a certain demographic (for example, those with a family history of preexisting hypertension or pre-sexual pre-lampsia) are known to be at a moderate risk of developing the condition, he says. Morten Rasmussen At Mirvie. But for many, it comes from the blue at first glance.

Once someone knows that they are at high risk of pre-lamps, they can take action to prevent this. Common interventions include taking medications like aspirin, switching to a Mediterranean diet, and monitoring your daily blood pressure.

However, the new test only looked at people between 17.5 and 22 weeks after pregnancy. “Ideally, you should start aspirin 16 weeks in advance.” Kathryn Gray At Washington University in Seattle. “So by the time most people get the results of this test, they’ve already missed that window.”

Mirvie plans to sell blood tests on the market soon. Once it’s on the market, the team hopes other scientists will use it to develop drugs that specifically target the expression of genes such as PAPPA2. Such molecular pinpoints “give a much better opportunity for treatment to be effective,” says Rasmussen.

Gray also hopes researchers will use Mirvie’s RNA bank data to further identify the genes behind the risk of prelammosis in certain people. She says narrowing down your search profile could reduce the cost of testing and make it affordable for more people.

The article was revised on April 8, 2025

This article has been revised to reflect the risks posed by pre-lammosis during pregnancy

The article was revised on April 10, 2025

We have revealed that the test has identified people at risk of developing pre-lammosis.

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Source: www.newscientist.com

RNA blood tests can predict the risk of pre-eclampsia

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Pre-Lamp Disease is a potentially serious complication of pregnancy

Half Point Image/Getty Image

Pre-lamp syndrome can lead to many pregnancy complications, including death, but can be difficult to detect in the early stages of pregnancy. New blood tests can help doctors identify the risk of developing a pregnant individual’s condition before symptoms begin.

“We can narrow it down to four really high-risk pregnancies. That’s a big step.” Maneesh Jain at Mirvie, a California-based health startup.

Pre-salping syndrome is a type of hypertensive disorder (HDP) during pregnancy, which occurs when scientists are not sure exactly – occurs during placenta development. This can lead to high blood pressure and lead to cardiovascular disease, organ damage, seizures and even death. It can also cause harm to the developing fetus.

However, catching pre-lammosis and other HDP is difficult. This is because symptoms usually do not appear for at least 20 weeks after pregnancy. Sometimes, no signs are detected until work. It is difficult to monitor placenta development. This is because taking tissue samples from organs is very invasive.

New blood tests are relatively non-invasive and use RNA markers to predict whether someone may develop HDP. Specifically, this test focuses on specific genes PAPPA2 and CD163its overexpression was previously linked to HDP. The researchers wanted to see if they could detect this overexpression of blood samples.

Their validation studies of over 9,000 pregnant people suggest that they can: Jain says the test can be predicted with accuracy of over 99%, whether people without existing risk factors overexpress the gene and therefore are at a higher risk of EC presymptom or another HDP. Almost a quarter of participants without existing HDP risk factors overexpressed the gene.

People with a certain demographic (for example, those with a family history of preexisting hypertension or pre-sexual pre-lampsia) are known to be at a moderate risk of developing the condition, he says. Morten Rasmussen At Mirvie. But for many, it comes from the blue at first glance.

Once someone knows that they are at high risk of pre-lamps, they can take action to prevent this. Common interventions include taking medications like aspirin, switching to a Mediterranean diet, and monitoring your daily blood pressure.

However, the new test only looked at people between 17.5 and 22 weeks after pregnancy. “Ideally, you should start aspirin 16 weeks in advance.” Kathryn Gray At Washington University in Seattle. “So by the time most people get the results of this test, they’ve already missed that window.”

Mirvie plans to sell blood tests on the market soon. Once it’s on the market, the team hopes other scientists will use it to develop drugs that specifically target the expression of genes such as PAPPA2. Such molecular pinpoints “give a much better opportunity for treatment to be effective,” says Rasmussen.

Gray also hopes researchers will use Mirvie’s RNA bank data to further identify the genes behind the risk of prelammosis in certain people. She says narrowing down your search profile could reduce the cost of testing and make it affordable for more people.

The article was revised on April 8, 2025

This article has been revised to reflect the risks posed by pre-lammosis during pregnancy

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Source: www.newscientist.com