What sort of omniscient designer would make a cell dependent on a molecule that, when allowed to accumulate, can damage its energy-generating machinery? Presumably, one who could foresee the problem would also be capable of avoiding it. Yet research from Texas A&M University reveals precisely this vulnerability: RNA, indispensable to the functioning of living cells, can interfere with mitochondrial energy production when its abundance escapes normal control.
The findings, published in Proceedings of the National Academy of Sciences (PNAS) concern the relationship between RNA turnover and mitochondrial function. Messenger RNA carries instructions used to manufacture proteins, but those messages must also be broken down. The researchers found that this disposal process does more than regulate gene expression: it helps protect the machinery that supplies much of a cell’s usable energy.
Working with vaccinia virus, the team found that disrupting the breakdown of RNA allowed it to accumulate and severely impaired mitochondrial respiration. Further experiments showed that excess messenger RNA and double-stranded RNA could impair mitochondria even outside intact cells. The effect therefore did not require the usual antiviral immune responses. Excess RNA reduced mitochondrial membrane potential, a crucial component of the energy gradient used to make ATP. Precisely how RNA produces this disruption remains to be established.
This is not a case of cells having no safeguards. They have elaborate systems for controlling RNA abundance. The difficulty for intelligent design is that an essential component can become a threat to another essential component, leaving the cell dependent on continual regulation and clearance. Calling the safeguards evidence of brilliant design merely invites the question of why an all-knowing, all-powerful designer chose an arrangement with this vulnerability in the first place.
There is no comparable puzzle for evolution. Natural selection has no foresight, no drawing board and no opportunity to start again with an entirely different biochemistry. It acts on heritable variation in existing systems, favouring changes whose effects improve reproductive success under prevailing conditions. Benefits can outweigh costs without eliminating them, and a mechanism that works adequately under ordinary circumstances can remain vulnerable when conditions change. This study illustrates such a vulnerability; it does not establish the precise historical trade-offs that produced it.
There is an additional irony. Poxviruses also benefit from RNA clearance because they depend on the infected cell’s machinery to reproduce. Keeping that machinery functioning can serve the parasite as well as the host. This makes sense as the outcome of competing evolutionary interests. For anyone insisting that a benevolent, omniscient designer deliberately planned the entire arrangement, however, both the vulnerability and its exploitation require rather more explanation.
Why cells must destroy the RNA they need. RNA is indispensable to life, but a cell cannot function simply by making it and allowing it to accumulate. Healthy cells continually produce, use and dismantle RNA. Maintaining the appropriate balance — known as RNA homeostasis — is an essential part of regulating their activity.The paper in PNAS was announced in a Texas A&M University news report:
Why RNA is essential
Messenger RNA (mRNA) carries information copied from DNA to the ribosomes, where that information is used to assemble proteins. Other types of RNA help to build the ribosomes, deliver amino acids during protein synthesis, or regulate gene activity. Some RNA molecules even catalyse chemical reactions.
Different RNAs have different working lifetimes. Some remain functional for relatively long periods, while others are rapidly broken down. This variation is part of how cells control their internal chemistry.
Why messages need an expiry date
An mRNA molecule can be read repeatedly to produce multiple copies of a protein. Its abundance and lifespan therefore help determine how much of that protein a cell makes. Removing messages that are no longer needed allows the cell to change its protein production as conditions change.
RNA degradation also provides quality control. Defective or incorrectly processed messages can interfere with normal protein production, so cells have mechanisms that recognise and remove many of them. RNA disposal is therefore part of normal cellular function, rather than merely an emergency response.
How cells clear away RNA
Enzymes called ribonucleases cut RNA into smaller pieces or dismantle it progressively from its ends. For many cellular mRNAs, degradation involves shortening a protective tail or removing a protective cap before further breakdown. The resulting components can enter cellular recycling pathways.
These processes are regulated: a cell must retain useful RNA long enough for it to do its job while preventing unwanted molecules from accumulating.
What has this to do with energy?
Mitochondria produce much of the ATP used by many of our cells. Their respiratory machinery establishes an electrochemical gradient across the inner mitochondrial membrane. The flow of protons back across that membrane through ATP synthase helps drive ATP production.
The Texas A&M study found that excessive RNA accumulation can impair mitochondrial respiration and reduce membrane potential. Experiments with isolated mitochondria showed that the effect did not require an intact cell or its antiviral immune response. The precise molecular interactions responsible remain under investigation.
Why viruses complicate the balance
Viral infection can alter both RNA production and its removal. Vaccinia virus produces enzymes that help accelerate RNA degradation in cooperation with the host cell’s machinery. When this clearance was disrupted in the experiments, RNA accumulated and mitochondrial function deteriorated.
As the university’s account explains, maintaining a functioning host cell can also benefit the virus, which depends on that cell for energy and protein production. RNA clearance can therefore support cellular function while also helping an infection to continue.
Brief glossary
- mRNA:
- Messenger RNA; a temporary template used to make a protein.
- RNA degradation:
- The enzymatic breakdown of RNA.
- Mitochondria:
- Cellular structures with major roles in energy metabolism.
- ATP:
- Adenosine triphosphate; a molecule whose chemical reactions supply usable energy for many cellular processes.
- Homeostasis:
- The active maintenance of internal conditions within a functional range.
Too much RNA can starve cells of energy, study finds
Researchers uncover a link between excess RNA and mitochondrial damage — revealing new insights into viral infections, aging and RNA-based therapeutics.
A new study from researchers at the Texas A&M College of Veterinary Medicine and Biomedical Sciences (VMBS) has uncovered a previously unknown consequence of viral infection: too much RNA inside a cell can disrupt its ability to produce energy.
Published in the journal Proceedings of the National Academy of Sciences, the study found that when excess RNA builds up inside cells during poxvirus infection, it can impair mitochondria — the structures responsible for generating most of a cell’s energy — reducing the cell’s ability to function normally.
The discovery could have broad implications for understanding viral infections, aging-related diseases, and RNA-based therapeutics, including mRNA vaccines, because excess RNA can accumulate in each of these conditions.
Scientists have long known that RNA degradation helps control protein production and remove defective RNA. Our study reveals another important role: it helps cells maintain the energy they need to function properly.
Professor Dr. Zhilong Yang, senior author
Department of Veterinary Pathobiology
College of Veterinary Medicine and Biomedical Sciences
Texas A&M University, TX, USA.
The findings suggest that RNA degradation serves a broader purpose than scientists once realized. In addition to controlling protein production, RNA quality control, and helping cells regulate immune responses, it also helps protect the cell’s ability to generate energy.
When RNA builds up inside cells
RNA exists in many forms. Messenger RNA (mRNA) carries the genetic instructions the cells use to make proteins, which help cells perform their normal functions. Another form, double-stranded RNA (dsRNA), is commonly produced during viral infections and alerts the immune system that something is wrong.
During viral infection, viruses can produce large amounts of RNA. If cells cannot break down the excess RNA quickly enough, the buildup can damage mitochondria and reduce the cell’s ability to generate energy.
While scientists already know that excess dsRNA can trigger immune responses and the cell’s need to control dsRNA levels, the effects of mRNA came as a surprise.
MRNA is a normal component of our cells, but it seems like with many good things, if we get too much, that can become a problem for the cell. When too much RNA builds up, including mRNA, it can damage the mitochondria and interfere with the cell’s ability to produce energy.
Professor Dr. Zhilong Yang.
Viruses, meanwhile, rely entirely on host cells for energy and protein production, but producing too much viral RNA can overwhelm the very cells viruses depend on to survive.
Yang explained that poxviruses — the family of viruses that includes smallpox and mpox — appear to use RNA cleanup systems to degrade RNAs and keep infected cells functioning long enough for the virus to continue replicating.
If the cell is not healthy, the virus would not replicate well. The virus needs to keep RNA levels balanced inside the cell.
Professor Dr. Zhilong Yang.
A novel effect on mitochondria
The researchers initially thought the mitochondrial damage was likely caused by immune responses triggered by excess RNA, since certain forms of RNA are known to alert the body’s defenses during infection.
When we isolated only the mitochondria and added RNA, we still saw mitochondrial damage. That was the moment we realized this could be a previously unknown cellular response to RNA.
Dr. Djamal Brahim Belhaouari, first author,
Department of Veterinary Pathobiology
College of Veterinary Medicine and Biomedical Sciences
Texas A&M University, TX, USA.
The team also found that mitochondrial impairment occurred before major immune responses were activated and did not depend on the immune system’s usual response to infection, further supporting the idea that RNA itself contributes to the damage.
We think the negatively charged RNA may accumulate around mitochondria and disrupt the electrical balance needed for energy production, although how it happens is unknown. This is a new concept that we are continuing to explore.
Professor Dr. Zhilong Yang.
Implications beyond viral infection
The findings may also have implications beyond viral infections.
Researchers have observed RNA accumulation in a variety of conditions — including some cancers, neurodegenerative diseases, and aging-related disorders — suggesting that mitochondrial damage may be one way excess RNA contributes to those conditions.
We think this has quite broad translational implications. Too much double-stranded RNA or mRNA that cannot be degraded effectively may contribute to disease processes in some contexts.
Dr. Djamal Brahim Belhaouari.
The study may also provide new insight into RNA-based therapeutics and vaccines by helping scientists better understand how cells respond to large amounts of RNA and may eventually help improve future RNA-based treatments.
Understanding this mechanism could help researchers design and optimize future RNA-based therapeutics and vaccines by better understanding how cells respond to large amounts of RNA.
Professor Dr. Zhilong Yang.
The researchers say the findings could reshape how scientists think about the relationship between RNA regulation and cellular energy production.
Scientists already knew that too much double-stranded RNA can be harmful. What surprised us was finding out that too much mRNA — something cells normally need every day — can also damage mitochondria and interfere with the cell’s ability to produce energy.
Professor Dr. Zhilong Yang.
Publication:
What emerges from this research is a cellular system whose functioning depends on maintaining a balance between essential activities and potentially damaging consequences. RNA is indispensable, yet its excessive accumulation can compromise the machinery that supplies usable energy. The mechanisms that control it are effective enough to sustain life, but they remain vulnerable to disruption. That is entirely consistent with evolution working through modifications of existing biochemistry, without foresight or any guarantee of perfection.
Natural selection does not calculate future risks or anticipate every possible infection. It favours heritable changes that improve reproductive success under the conditions in which they arise. Benefits can outweigh costs while leaving weaknesses unresolved. Although this study does not reconstruct the evolutionary history of RNA regulation, the vulnerability it reveals fits comfortably within that framework. There is no requirement for an evolved system to be immune to every consequence of its own chemistry.
For advocates of an omniscient, omnipotent designer, however, the questions are more awkward. Such a designer could hardly have been surprised by the interaction between RNA and mitochondria. Nor could it plead that it was constrained by inherited machinery or unable to anticipate viral exploitation. Pointing to the sophistication of RNA clearance does not explain why a supposedly perfect creator chose a system in which an essential molecule becomes damaging when that clearance fails. The safeguards and the vulnerability must both be included in any honest assessment of the alleged design. What ID advocates are left with, if they insist on intelligent design, is incompetence or malevolence.
The viral dimension makes the difficulty sharper still: maintaining the infected cell’s energy supply can help its parasite reproduce. Evolution accommodates these competing interests without difficulty, because neither host nor virus is working towards a universal good. Meanwhile, the researchers have uncovered another testable relationship between cellular processes, opening further questions about how it works. Invoking a designer adds no mechanism, makes no useful prediction and leaves the central problem untouched: why would unlimited foresight produce such a precarious arrangement?
Advertisement
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
All titles available in paperback, hardcover, ebook for Kindle and audio format.
Prices correct at time of publication. for current prices.
No comments :
Post a Comment
Obscene, threatening or obnoxious messages, preaching, abuse and spam will be removed, as will anything by known Internet trolls and stalkers, by known sock-puppet accounts and anything not connected with the post,
A claim made without evidence can be dismissed without evidence. Remember: your opinion is not an established fact unless corroborated.