Nov. 6, 2013 — RNA is the key functional component of spliceosomes, molecular machines that control how genes are expressed, report scientists from the University of Chicago online, Nov. 6 in Nature. The discovery establishes that RNA, not protein, is responsible for catalyzing this fundamental biological process and enriches the hypothesis that life on earth began in a world based solely on RNA.
"Two of the three major processes in eukaryotic gene expression -- splicing and translation -- are now shown to be catalyzed by RNA," said Jonathan Staley, PhD, associate professor of molecular genetics and cell biology at the University of Chicago and co-corresponding author on the study. "The eukaryotic gene expression pathway is more of an RNA-based pathway than protein-based."
For genes to be expressed, DNA must be translated into proteins, the structural and functional molecules that catalyze chemical reactions necessary for life. To do so, genetic information stored in DNA is first copied into strands of messenger RNA (mRNA), which are subsequently used to create proteins.
In eukaryotes, almost all genes undergo alternative splicing, in which a precursor form of mRNA is cut and re-stitched together in numerous different combinations. This significantly increases the number of proteins a single gene codes for, and is thought to explain much of the complexity in higher-order organisms. Splicing is a critical biological mechanism -- at least 15 percent of all human diseases are due to splicing errors, for example.
Spliceosomes, made from proteins and short, noncoding RNA fragments, carry out splicing via catalysis, which in biological processes is usually attributed to protein-based enzymes. However, previous research has hinted that RNA in the spliceosome might be responsible. Despite decades of study, this question has thus far remained unanswered.
To address this, Staley and Joseph Piccirilli, PhD, professor of biochemistry and molecular biology and chemistry at the University of Chicago, partnered with graduate students Sebastian Fica and Nicole Tuttle, co-lead authors on the study.
The researchers first disabled the ability of the spliceosome to self-correct errors in splicing. They then modified single atoms at sites on mRNA precursors known to be cut during splicing, as well as several on U6, an RNA subunit of the spliceosome hypothesized to be important for catalysis. Some of these modifications rendered splicing ineffective. They went through and systematically rescued this loss-of function, investigating sites individually and in combination. This allowed them to hone in on locations critical to splicing function and to identify connections between U6 and mRNA precursors.
The team found that the U6 RNA subunit directly controls catalytic function -- effectively acting as the blade of the spliceosome. This is the first experimental proof that RNA is the key functional component of this critical biological mechanism.
They also found remarkable similarities in structure and function between spliceosome RNAs and group II introns, an evolutionarily-ancient class of self-splicing, catalytic RNA found in all major branches of life. They believe this indicates that these two RNA-based splicing catalysts share a common evolutionary origin, providing further evidence that key modern RNA-protein complexes, including the spliceosome and the ribosome, evolved from an RNA world.
"In modern life, protein enzymes catalyze most biological reactions," Piccirilli said. "The finding that a system like the spliceosome, which contains more protein than RNA, uses RNA for catalysis and has a molecular ancestor composed entirely of RNA suggests that the spliceosome's reaction center may be a molecular fossil from the 'RNA World.'"
RNA Controls Splicing: Implications for Origin of Life on Earth
RNA is a crucial part of life and now, scientists have discovered a little bit more about its importance. It turns out that RNA is the key functional component of spliceosomes, molecular machines that control how genes are expressed. The findings point to the hypothesis that life on Earth began in a world based solely on RNA. (Photo : AFTA)
RNA is a crucial part of life and now, scientists have discovered a little bit more about its importance. It turns out that RNA is the key functional component of spliceosomes, molecular machines that control how genes are expressed. The finding establishes that RNA and not protein is responsible for catalyzing this fundamental biological process. Not only that, it points to the hypothesis that life on Earth began in a world based solely on RNA.
For genes to be expressed, DNA must be translated into proteins, the structural and functional molecules that catalyze chemical reactions necessary for life. In order to do so, genetic information stored in DNA is first copied into strands of messenger RNA (mRNA) which are then used to create proteins.
In eukaryotes, almost all genes undergo alternative slicing. This process involves a prescursor form of mRNA being cut and re-stitched together in numerous different combinations. This increases the number of proteins a single gene codes for and could explain much of the complexity in higher-order organisms.
Spliceosomes, made from proteins and short, noncoding RNA fragments, actually carry out splicing via catalysts. However, previous research has hinted that RNA in the spliceosome might be responsible. In order to find out whether or not this is true, though, researchers decided to investigate a bit further.
The scientists first disabled the ability of spliceosomes to self-correct errors in splicing. They then modified single atoms at sites on mRNA precursors known to be cut during splicing, as well as several on U6, an RNA subunit of the spliceosome hypothesized to be important for catalysis. Some of these modifications rendered splicing to be ineffective. After systematically rescuing this loss-of function, the researchers were able to hone in on locations critical to splicing function.
In the end, the scientists found that the U6 RNA subunit directly controls catalytic function. It effectively acts as the blade of the spliceosome. This particular finding is the first experimental proof that RNA is the key functional component of this critical biological mechanism.
"In modern life, protein enzymes catalyze most biological reactions," said Joseph Piccirilli, one of the researchers, in a news release. "The finding that a system like the spliceosome, which contains more protein than RNA, uses RNA for catalysis and has a molecular ancestor composed entirely of RNA suggests that the spliceosome's reaction center may be a molecular fossil from the 'RNA World.'"
The findings are published in the journal Nature.
Quest for self-replicating RNA edges closer to life’s possible origin
RNA can't copy itself, but can copy over 200 bases of other RNAs.
by John Timmer - Oct 25 2013, 10:00pm IST
The discovery of nucleic acid molecules that can catalyze chemical reactions has revolutionized thinking about the origin of life. These catalytic RNAs, called ribozymes, showed that a single molecule could embody two of the major aspects of life: genetic information and chemical activity. They also raised the intriguing possibility that it might be possible to find an RNA molecule that could copy itself. After all, once you have a single self-duplicating molecule, you would quickly end up with a large collection of self-duplicating molecules competing for resources. Evolution would be off and running.
So far, though, efforts to make a self-replicating ribozyme have come up short. Most RNA molecules with this sort of activity have been around 200 bases long and have tended to stall before copying more than a few dozen bases. But now, scientists have produced the first molecule that can copy RNAs longer than itself. The scientists found it by selecting for RNAs that work in conditions that are normally the death of biochemical activity: sub-zero mixtures of ice and water.
Makin’ copies
The path to a potential self-replicating RNA has, so far at least, been a bit convoluted. Starting with a collection of RNA molecules with random sequences, researchers come up with a ribozyme that could link two RNAs together (termed a ligase). Rounds of mutation meant to improve that activity succeeded in doing so, but they also popped out a different class of molecules entirely; they could make copies of a specific group of short sequences. Further experiments with mutation and selection made these catalytic RNAs work more generally and extended the molecules they could copy to longer sequences. But the RNAs themselves were over 200 bases long, and they tended to fall short of copying molecules that were much smaller than that.
The Cambridge researchers behind the new paper noticed something unusual. Although this catalytic RNA was originally evolved to work at room temperature, it worked even better on ice. Ice tends to slow down reactions, but partly freezing a solution will cause the remaining salts and RNA to concentrate in the gaps between the frozen ice. A network of water-filled crevices tends to form, and the water within them stays liquid to well below 0°C, giving the ribozymes something to work with. (Environments like this currently exist in polar regions.)
If the ribozyme worked well on ice as-is, the authors reasoned that it would work even better with a chance to adapt to the cold environment. So they subjected the ribozyme to a few rounds of mutation, followed by selection for its ability to copy RNA molecules in an icy environment. The RNA they produced this way not only worked better in the cold environment, but it was more active in all conditions tested, including in temperatures up to 27°C.
That increased activity produced the ability to copy longer RNA molecules for the first time. In fact, the paper's authors were able to get their ribozyme to copy one that was 206 bases long, while the RNA that did the copying was only 202 bases long.
It's great progress, but the result still comes far short of a molecule that can copy itself. For one thing, the ribozyme tended to stop short of the end of the molecule it was copying, mostly because the two fell out of contact. The authors could tether the two RNA molecules (the ribozyme and the template it was copying) together, which improved matters but didn't solve the problem entirely. The second problem was the fact that the molecule being copied folded over and formed base pairs with itself, which prevented the ribozyme from copying through the folded structure.
This creates a serious problem since the activity of the ribozyme depends on it being able to fold into a three-dimensional structure—which creates a bit of a chicken-and-egg problem for making a self-replicating ribozyme.
The authors suggest that the way around this issue might be to make the molecule even longer. If they could find a ribozyme that disrupts these folds, it might be possible to link it to the one that does the copying. Combined, the two may be able to work their way through copies of even large molecules. Ultimately, this could be the route to building the first self-copying genetic molecule.
Nature Chemistry, 2013. DOI: 10.1038/NCHEM.1781 (About DOIs).
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Scientists Solve Major Piece in the Origin of Biological Complexity
Nov. 6, 2013 — Scientists have puzzled for centuries over how and why multicellular organisms evolved the almost universal trait of using single cells, such as eggs and sperm, to reproduce. Now researchers led by University of Minnesota College of Biological Sciences postdoctoral fellow William Ratcliff and associate professor Michael Travisano have set a big piece of that puzzle into place by applying experimental evolution to transform a single-celled algae into a multicellular one that reproduces by dispersing single cells.
"Understanding the origins of biological complexity is one of the biggest challenges in science," Travisano said. "In this experiment we've reordered one of the first steps in the origin of multicellularity, showing that two key evolutionary steps can occur far faster than previously anticipated." (Credit: © abhijith3747 / Fotolia)
"Until now, biologists have assumed that this single-cell bottleneck evolved well after multicellularity, as a mechanism to reduce conflicts of interest among the cells making up the organism," says Ratcliff. "Instead, we found that it arose at the same time as multicellularity. This has big implications for how multicellular complexity might arise in nature, because it shows that this key trait, which opens the door to evolving greater multicellular complexity, can evolve rapidly."
In an article published today in the journal Nature Communications, the researchers described how they produced the multi-celled strain by repeatedly selecting and culturing algae that settled quickly to the bottom of a liquid-filled test tube. After 73 rounds, they discovered that the algae in one of the tubes had gone multicellular.
Observing the new form, Ratcliff and Travisano discovered that it reproduced by actively breaking up, shedding motile single cells that go on to grow into new multicellular clusters. They developed a mathematical model that explained the reproductive benefit of this single-celled strategy over hypothetical alternatives in which the cluster would produce larger propagules. The model predicted that reproduction from single cells would be more successful in the long run. Even though single cells are less likely to survive than larger propagules, this disadvantage is more than made up for by their sheer number.
In collaboration with Matthew Herron and Frank Rosenzweig at the University of Montana, the researchers are now working to find the genetic basis for multicellularity and experimentally evolve even greater multicellular complexity.
"Understanding the origins of biological complexity is one of the biggest challenges in science," Travisano said. "In this experiment we've reordered one of the first steps in the origin of multicellularity, showing that two key evolutionary steps can occur far faster than previously anticipated. Looking forward, we hope to directly investigate the origins of developmental complexity, or how juveniles become adults, using the multicellular organisms that we evolved in the lab."
Several years ago, Travisano and Ratcliff made international news when they evolved multicellularity in yeast. This work takes those findings further by initiating multicellularity in an organism that has never had a multicellular ancestor and provides a new hypothesis for the evolutionary origins of the single-cell bottleneck in multicellular life cycles.
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The above story is based on materials provided by University of Minnesota.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
- William C. Ratcliff, Matthew D. Herron, Kathryn Howell, Jennifer T. Pentz, Frank Rosenzweig, Michael Travisano. Experimental evolution of an alternating uni- and multicellular life cycle in Chlamydomonas reinhardtii. Nature Communications, 2013; 4 DOI: 10.1038/ncomms3742
Texas Researcher Explains Evolution of Life
Oct 30, 2013 09:23 AM EDT
(Photo : wikimedia creative commons)
Texas Tech University researcher says that meteorites that hit early earth kick-started life and complex forms took birth in the deep craters formed by the impact.
Origin of life on earth is a mystery that still baffles science. Many theories have been proposed to explain the origins of biological forms. However, none of them independently explain the start of life.
Now, Sankar Chatterjee, Horn Professor of Geosciences and curator of paleontology at the Museum of Texas Tech University, says that he has connected the dots and found how life may have originated.
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The idea of life coming from elsewhere isn't new. For decades, it has been hypothesized that life might have originated at some other place in the Universe and accidently landed on Earth.
Ancient craters on Venus and Mars describe the struggle that the planets had to go through during their infant years.
Chatterjee's research suggests meteorites got the essential ingredients to life-building from the distant corners of the Universe.
"When the Earth formed some 4.5 billion years ago, it was a sterile planet inhospitable to living organisms," Chatterjee said in a news release. "It was a seething cauldron of erupting volcanoes, raining meteors and hot, noxious gasses. One billion years later, it was a placid, watery planet teeming with microbial life - the ancestors to all living things."
According to Chatterjee, life began in four steps. It went from cosmic, geological, chemical and arrived at its biological state.
The Cosmic Stage-
Between 4.1 to 3.8 billion years ago, earth was pounded daily by large meterorites. These rocks punched holes in the crust and created geothermal vents. Also, essential life ingredients from other parts of the Universe arrived on earth via these meteorites.
Recently, astronomers have found asteroids could even act as water-delivery systems.
Chaterjee studied fossil-rocks in Greenland, Australia and South Africa and believes that these might have been the places where life first appeared.
The Geological Stage-
Icy comets that came to earth melted due to earth's perfect proximity to the sun. The geothermal vents then heated these water-filled craters and created a thick primordial soup.
"The geological stage provides special dark, hot, and isolated environments of the crater basins with the hydrothermal vent systems that served as incubators for life," he said. "Segregation and concentration of organic molecules by convective currents took place here, something like the kinds we find on the ocean floor, but still very different. It was a bizarre and isolated world that would seem like a vision of hell with the foul smells of hydrogen sulfide, methane, nitric oxide and steam that provided life-sustaining energy."
The Chemical and Biological Stage-
In this stage, the chemicals in the water reacted and formed simple organic molecules.
One can create organic molecules in the lab, but not life. Chaterjee said that the ancient soup had a key biological ingredient- fatty lipid material, which came to earth on space body. Complex biological forms that had the ability to replicate underwent many trials and errors.
"The emergence of the first cells on the early Earth was the culmination of a long history of prior chemical, geological and cosmic processes," he said.
© Copyright 2013 Nature World News. All Rights Reserved.
ndian-origin scientist reveals 'how life began on Earth more than 3.8 billion years ago'
Sunday, Nov 3, 2013, 12:03 IST | Place: Washington, DC | Agency: ANI
He believes that meteorites deposited organic materials in them and then icy comets that crashed into Earth melted, and filled them with water.
Indian-origin paleontologist, Dr. Sankar Chatterjee, believes that he has found the answer to the question about how life on Earth began more than 3.8 billion years ago.
Chatterjee, a professor of geoscience at Texas Tech University and curator of paleontology at the Museum Of Texas Tech University argues that in addition to bringing water and the chemical constituents of life, asteroids and meteors made impact craters that became “crucibles” in which chemical reactions that ultimately gave rise to living cells took place, the Huffington Post reported.
He believes that meteorites deposited organic materials in them and then icy comets that crashed into Earth melted, and filled them with water.
He said that additional meteorite strikes made volcanically driven geothermal vents in the Earth’s crust that heated and stirred the water.
The “primordial soup” then mixed the chemicals together and led to the formation of molecules of ever increasing complexity — and eventually life.
To arrive at this result, Chatterjee studied sites that contained world’s oldest fossils in Greenland, Australia, and South Africa.
Washington, November 4, 2013
Updated: November 4, 2013 02:27 IST
India-origin scientist explains how life began on earth
PTI
Dr. Sankar Chatterjee. Picture courtesy: Texas Tech University
Palaeontologist Sankar Chatterjee claims he has found the answer to how life began on earth
An Indian-origin scientist claims to have solved the mystery of how life on earth exactly began about 4 billion years ago after studying three sites containing the world’s oldest fossils.
According to Sankar Chatterjee, a Texas Tech University palaeontologist, meteorite bombardment left large craters on earth that contained water and chemical building blocks for life, which ultimately led to the first organisms.
How life began on earth has baffled humans for millennia.
Dr. Chatterjee, who was born in Kolkata, believes he has found the answer by connecting theories on chemical evolution with evidence related to our planet’s early geology. “This is bigger than finding any dinosaur. This is what we have all searched for — the Holy Grail of science,” he said.
Thanks to regular and heavy comet and meteorite bombardment of earth’s surface during its formative years 4 billion years ago, the large craters left behind not only contained water and the basic chemical building blocks for life, but also became the perfect crucible to concentrate and cook these chemicals to create the first simple organisms. Dr. Chatterjee’s research suggests meteorites can be givers of life as well as takers. He said it was likely that meteor and comet strikes brought the ingredients and created the right conditions for life on our planet.
By studying three sites containing the world’s oldest fossils, he believes he knows how the first single-celled organisms formed in hydrothermal crater basins. “When the earth formed some 4.5 billion years ago, it was a sterile planet inhospitable to living organisms,” Dr. Chatterjee said, going on to add: “It was a seething cauldron of erupting volcanoes, raining meteors and hot, noxious gasses. One billion years later, it was a placid, watery planet teeming with microbial life — the ancestors to all living things.”
Dr. Chatterjee presented his findings at the Annual Meeting of the Geological Society of America in Denver.
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