In New Research, RNA Takes Center Stage
Here is a survey of important new discoveries about RNA (ribonucleic acid). RNA differs from DNA by one little change — the sugar ribose (with an OH group at the carbon-2) instead of deoxyribose (with just H there). This makes a big difference in the structural and functional traits of RNA. Unlike DNA, RNA is less durable, and often single-stranded. It also pairs to adenine (A) with uracil (U) instead of thymine (T), which has a methyl group at the carbon-5 position instead of uracil’s hydrogen.
These differences, though slight, make each nucleic acid perfectly suited for its respective roles in the cell. Long thought to be a mere template for transcription and translation of DNA with the names messenger RNA (mRNA) and transfer RNA (tRNA), RNA with its more transient lifetime serves many other functions that have been coming to light in the 21st century. New terms are being added to the vocabulary of epigenetics: among them, long noncoding RNA (lncRNA), micro-RNA (miRNA), dietary RNA, and extracellular RNA (exRNA).
Thousands of Designs
RNA can fold in complex ways. Researchers at Ruhr-Universität Bochum are looking for unknown RNA structures among the thousands of RNA molecules in cells, expecting that many of the folded RNAs will prove functional, just like proteins are. The scientists are using a new technique called lead sequencing to identify RNA structures: “No structure — no function.”
In all living cells, genetic information is stored in double-stranded DNA and transcribed into single-stranded RNA, which then serves as a blueprint for proteins. However, RNA is not only a linear copy of the genetic information, but often folds into complex structures. The combination of single-stranded and partially folded double-stranded regions is of central importance for the function and stability of RNAs. “If we want to learn something about RNAs, we must also understand their structure,” says Franz Narberhaus. [Emphasis added.]
One such function that they mention: RNA as a thermometer! Some RNAs will change their structure depending on the temperature. One example provided in the press release involves the diarrhea pathogen Yersinia pseudotuberculosis. An RNA thermometer allows the parasite to detect whether it is inside the host — a useful function for the germ, but not its victim. “Using lead sequencing, the team not only identified already known RNA thermometers, but also discovered several new ones.” Hopefully some more salutary instances of this capability will be identified in their work.
RNA for Pipeline Monitoring
Micro-RNAs have been implicated as protectors of vascular integrity, says Ludwig-Maximilian University of Munich. They found “a hitherto unknown molecular function of a specific microRNA that preserves integrity of the endothelium and reduces the risk of atherosclerosis.” One micro-RNA (miRNA) in particular shifts the RNA paradigm; it doesn’t go out of the nucleus; it goes back in, bearing a message.
Short RNA molecules known as microRNAs (miRNAs) play a vital role in the regulation of gene expression. Anomalies in miRNAs expression and function have been implicated in pathological processes, such as the development of chronic diseases like atherosclerosis. The regulatory functions of miRNAs usually take place in the cytoplasm, where they interact with target RNA transcripts to inhibit their translation into protein or promote their decay. However, Professor Christian Weber’s group in the Institute for Cardiovascular Prevention (IPEK) at the LMU Medical Center has now described an exceptionally different mode of action. By investigating a miRNA named miR-126-5p, Weber’s team demonstrates that this molecule can unexpectedly be transferred into the cell nucleus and, by simply interacting with it, suppresses the activity of an enzyme, named caspase-3, which is responsible for killing the cell by programmed cell death. In this way, the molecule protects vascular integrity and reduces the extent of atherosclerotic lesions.
Cells lining the blood vessels often are subject to shear stress. Ordinarily, stress signals would initiate programmed cell death (apoptosis). This micro-RNA enters the nucleus and stops one of the executioner proteins named caspase-3, saying, in essence, “It’s OK; let the cell live.” This hitherto unknown function of miR-126-5p “represents a new principle of biological regulation that serves to complement previously well described mechanisms,” Weber said.
RNAs without Borders
There are “doctors without borders” who travel far from their countries to help patients in deprived areas around the globe. There are also “RNAs without borders” that leave their home cells to bring aid to tissues around the body. So fascinating is this new concept of “extracellular RNA” (exRNA), Nature devoted a special issue to the subject. Herb Brody writes,
The molecule best known for its part in translating genetic code into protein-assembly instructions is finding a new role in medicine. RNA, once thought to exist only in cells, is now known to travel to tissues all over the body through the blood, under the protection of tiny lipid sacs known as extracellular vesicles. The study of this extracellular RNA (exRNA) has led to a quiet revolution in biology, as scientists endeavour to understand why cells release RNA, and how the molecules might be used to improve the detection and treatment of disease.
In one example, RNA was discovered ten years ago in mother’s milk. Tien Nguyen says in Nature, “scientists are still trying to work out why they are there and how they affect health.” Micro-RNA (miRNA), “Once overlooked as genetic junk,” is proving its worth in many ways. “By attaching to matching strands of messenger RNA, which is involved in protein synthesis, miRNA can effectively turn mRNA off and on, and alter what proteins are made,” Nguyen adds. In the case of mother’s milk, one researcher started asking the right questions:
Bo Lönnerdal, a biochemist at the University of California, Davis, has spent decades studying the bioactive components of breast milk. When Lönnerdal learnt that researchers had found miRNAs in breast milk, he remembers wondering what the molecules were doing there. There must be a reason why these seemingly random bits of RNA are present in milk, he recalls thinking.
He wondered if the miRNAs provided nutrition, or were regulating some other substance. It’s a tedious process to solve — 1,400 miRNA’s have been identified in breast milk — but so far, it appears that these packages of code do regulate genes within the baby, perhaps tuning immune responses or speeding up rates of development for pre-term babies. Some miRNA might even be protecting against infant cancer. This is a cutting-edge field that scientists around the world are pursuing. Understanding the roles of miRNA in breast milk might lead to improved baby care.
Not Just for Babies
Adults also stand to benefit from understanding exRNA. In another article in the Nature special issue, Kenneth Witwer declares that “Dietary RNA is ripe for investigation,” because “RNA in food could have profound effects on the human digestive system and on health more generally.” Kristina Campbell explores the ferment arising from initial investigations of exRNA. In her Nature article, she asks, “Do the microRNAs we eat affect gene expression?” In other words, can genetic material be transferred to us from the food we eat? It’s too early to tell what roles dietary RNA play, but what a concept to think that food might be doing more than providing nutrients; it might also be adding genetic information about how to use those nutrients!
Because extracellular RNA is now known to travel throughout the body, future methods might be able to use them to diagnose disease. In his Nature article, Elie Golgin surveys the prospects for using exRNAs as markers for cancer, heart disease and other conditions.
The body’s tissues routinely communicate with each other through RNA messages sent back and forth between cells. So, it seemed obvious to scientists that, by eavesdropping on these extracellular communiqués carried in blood, saliva, urine and other fluids, they should be able to intercept dispatches indicative of health and disease.
The rest of the article describes how complicated that naïve hope is turning out to be. Nevertheless, “There’s tremendous growth in the field,” Golgin says, and “It’s driving companies now to commercialize a number of these approaches.” Elizabeth Svoboda elaborates on some of the work being done in her Nature article, “Research round-up: extracellular RNA.” This is clearly a very active field. Researchers may find new avenues for treatment of heart disease, neurodegenerative disorders, cancer, kidney regeneration, and even anxiety conditions like PTSD. Clinical trials are coming. Soon, an entirely new suite of therapies may add to the doctor’s toolkit, all based on the sequenced messages in RNA.
Life Is Message-Based
Even plants use RNA for messaging, reports Roxanne Khamsi in her Nature piece about RNA-containing vesicles in plants. If scientists can find ways to control the exosomes with their embedded genetic information packets, this might lead to farmers using crop sprays that contain RNA. And if plants and human beings are using RNA in many functional roles, it’s becoming clear that all organisms on the planet rely on these genetic molecules for many purposes.
A new window on intelligent design is opening wide. This revolution in RNA research might be comparable to previous revolutions that uncovered the functional roles of DNA and proteins. It’s noteworthy that mentions of evolution were non-existent in all these articles except one, and that one amounted to raw speculation:
[Janos] Zempleni says that “miRNAs and exosomes are way more bioavailable in milk than in plants”. He speculates that this might have evolutionary underpinnings: “Nature may have made them to be bioavailable because of infant nutrition,” he says.
That’s not even a Darwinian statement. Zempleni has just treated “nature” as a goddess with foresight, installing miRNAs for a purpose. In the same article, the only other mention of evolution was by Kenneth Witwer of Johns Hopkins School of Medicine, who speculated about non-evolution:
He remembers thinking, “maybe this is some evolutionarily conserved way that we can extract something else from our food other than just nutrition.”
Evolutionists have already failed this burgeoning field by relegating RNAs they didn’t understand to the “genetic junk” bin. And ever since, after all these years of discovery, all they can do is speculate about what “might have evolutionary underpinnings.” This is a great time for design advocates to read the messages in RNA and find out what they are saying.
Image: RNA molecules, via Illustra Media’s documentary Origin.