Look at All that Goes into Translating a Gene
Evolution News & Views
In Nature, Marlene Oeffinger gives readers a tour of the ribosome, in particular how it is built. This wonder of the cell translates messenger RNA into proteins. Prepare to be astonished. Here’s the overture:
Production of the cell's translational apparatus, the ribosome, requires the orchestrated function of hundreds of proteins. A structure of its earliest precursor yields unprecedented insight into ribosome formation. [Emphasis added.]
For the first movement, she calls forward an ensemble of scientists led by Markus Kornprobst. They published in the journal Cell a composition about the “pre-ribosome” in eukaryotes. The 3-D structure of this protein, revealed through cryo-electron microscopy, shows that it engulfs the “pre-rRNA” (one of the large, complex RNA molecules that will comprise the ribosome) during construction. The pre-ribosome itself has about 70 assembly factors. Are we sounding irreducibly complex yet? The work has only begun. Oeffinger comments,
The structure reveals, for the first time and in stunning detail, the arrangement of and interactions between many proteins that have been implicated in ribosome assembly, shedding light on a crucial step in early ribosome formation.
Keep in mind we are only looking so far at one crucial step in early ribosome formation.
In the nucleolus, three of four ribosomal RNAs undergo assembly before leaving to work in the cytoplasm. Many other proteins, called ribosome biogenesis factors, will be involved in construction of the pre-ribosome. (Remember, this is just for the pre-ribosome.) As the complexity grows, tension increases in the orchestration:
During its transcription, the long pre-rRNA is assembled with r-proteins, ribosome biogenesis factors and small nucleolar RNAs to form a large 90S pre-ribosome. Following the first stage of pre-rRNA processing, the complex splits into two pre-ribosomes, dubbed pre-40S and pre-60S, which are eventually exported to the cytoplasm where they undergo further maturation steps and then join as 40S and 60S subunits to form the mature ribosome.
Along with the identities of the biogenesis factors came the realization that they numbered a vast 200 to 300 in eukaryotes. In the yeast Saccharomyces cerevisiae, the 90S pre-ribosome alone contains about 70 ribosome biogenesis factors -- almost as many as the number of proteins in a mature ribosome. Hence, a recurring question in the field is: why does ribosome production require so many accessory proteins?
Kornprobst’s team provided a partial answer. All these dozens of proteins are involved in multi-part complexes that work together to build the pre-ribosome.
The requirement for so many extra proteins is explained by the authors' observation that many accessory proteins are arranged around the folded pre-rRNA molecule in previously defined multi-protein complexes called UTP-A, UTP-B and UTP-C. Of these, UTP-A and UTP-B form a scaffold, within which the newly transcribed pre-rRNA is encased and so can be securely processed, modified and assembled with r-proteins.
Explained, perhaps, but not simplified! Oeffinger’s cartoon illustration of these complexes shows the pre-rRNA being threaded into a mold formed by UTP-A, UTP-B, and another factor named U3. “Encased within this mould, the pre-rRNA is safely folded and processed,” she explains. But then, we still only have the Pre-40S and Pre-60S parts of the ribosome constructed.
The role of this scaffold is reminiscent of the way in which chaperone proteins aid folding of other proteins -- a common process that prevents aggregation of proteins into non-functional structures. But although chaperone-mediated protein folding has been long established, the idea of chaperone moulds is new to RNA biology.
Keep that in mind as we talk later about the implications for the origin of life. That little U3 factor, by the way, has two functions. Half of it forms part of the scaffold. The other half is buried deep within the pre-ribosome, “presumably interacting with the pre-rRNA.” It clings to a spacer molecule that gets cleaved from the pre-rRNA. This step “is crucial for the separation of the processed 90S pre-rRNAs into pre-40S and pre-60S complexes, and the progression of ribosome production.”
We’re getting into gory details on purpose. We need to hear the complex counterpoint going on, so that the standing ovation at the end of the composition will be deserved. Remember, we are still just trying to get the “pre-ribosome” finished. Bear with us:
Kornprobst and colleagues also identified the position of the pre-18S rRNA (which will become the rRNA component of the 40S subunit) in their structure. When comparing the pre-18S structure with that of the mature 18S rRNA, the authors observed that the molecule underwent progressive folding, beginning in the domains closest to the site where transcription began. In the 90S, these regions were folded to resemble the mature 18S, whereas domains farther from the transcriptional start site were seemingly still in transitory states. This observation fits well with a previous model of hierarchical rRNA assembly.
All this and we still don’t have a working ribosome yet -- just a pre-ribosome. At this point, though, we can give hearty applause for the first movement of the symphony. Oeffinger is sure thrilled with it.
Kornprobst and colleagues have visualized in detail what, until now, has been seen through electron microscopy only as small black balls on strings of pre-rRNA. Holding a magnifying glass to the early steps of ribosome biogenesis, the authors have finally revealed a role for the multitude of ribosome biogenesis factors as a chaperone mould that provides a secure environment for the processing and folding of pre-rRNA.
The rest of the story is bound to be good. For now, we can ponder these members of a large orchestra playing together, interacting in complex sequential ways, and ask some important questions. Chiefly, could any of this have arisen by chance?
Origin-of-life researchers sometimes leap from random building blocks to a cell, or a replicator, without considering all the factors involved. They think RNA is the magic molecule that can fulfill the dual roles of metabolism and coding. Simplistic accounts, like this one on Phys.org, make it seem an “RNA World” could have preceded the DNA-protein world of life as we know it.
Actual RNA, though, is extremely delicate and nearly impossible to form in water. With copious amounts of guidance and protection by intelligent investigators in a lab, RNA can do simple things like cut itself in half or make crude copies of parts of itself. What it cannot do is code for proteins that can help it assemble. That’s putting the cart before the horse. If it needs proteins to guide and protect it into a hierarchical sequence of stages leading up to a mature ribosome, you can’t invoke raw RNA as a stepping stone for what it has to have to exist.
And no fair attributing sentience to the RNA molecules. In a sense, they’re dumb. They have no goal, and no desire to organize on a cell-making project. Some origin-of-life researchers have a bad habit of envisioning the molecules wanting to get together to form a cell. RNA starts out holding some code and metabolic function, they will say, then it “hands off” the coding to DNA and the metabolism to proteins. For a materialist, that’s cheating.
Italian biochemist Pier Luigi Luisi calls the RNA World scenario a “baseless fantasy.” See his reasons in an interview with Susan Mazur in her book The Origin of Life Circus (pp. 360-363 in particular), where he dismisses it as so unrealistic on several levels that he states that a new start is needed, a “beginner’s mind revolution” away from the RNA-DNA-centric models.
The real problem is to make ordered sequences of amino acids, and of course ordered sequences of nucleic acids – and on that the prebiotic RNA world is absolutely silent. But this view of the prebiotic RNA world is still the most popular. I think it is a case of social science psychology more than science itself (p. 363).
We do know of a cause, however, that is capable of sequencing building blocks into ordered structures. It can organize dozens of complex parts that can interact in detailed ways, in a hierarchical structure, working in sequence toward a goal. That cause (need it be said again?) is intelligence.
Intelligence is not magic. It is a cause we know and use every day. It is a cause that is necessary and sufficient for these kinds of highly ordered operations. Because of this, and because blind chance is utterly incapable of such things, intelligence is the cause that we should use in our scientific explanations.
Evolution News & Views
In Nature, Marlene Oeffinger gives readers a tour of the ribosome, in particular how it is built. This wonder of the cell translates messenger RNA into proteins. Prepare to be astonished. Here’s the overture:
Production of the cell's translational apparatus, the ribosome, requires the orchestrated function of hundreds of proteins. A structure of its earliest precursor yields unprecedented insight into ribosome formation. [Emphasis added.]
For the first movement, she calls forward an ensemble of scientists led by Markus Kornprobst. They published in the journal Cell a composition about the “pre-ribosome” in eukaryotes. The 3-D structure of this protein, revealed through cryo-electron microscopy, shows that it engulfs the “pre-rRNA” (one of the large, complex RNA molecules that will comprise the ribosome) during construction. The pre-ribosome itself has about 70 assembly factors. Are we sounding irreducibly complex yet? The work has only begun. Oeffinger comments,
The structure reveals, for the first time and in stunning detail, the arrangement of and interactions between many proteins that have been implicated in ribosome assembly, shedding light on a crucial step in early ribosome formation.
Keep in mind we are only looking so far at one crucial step in early ribosome formation.
In the nucleolus, three of four ribosomal RNAs undergo assembly before leaving to work in the cytoplasm. Many other proteins, called ribosome biogenesis factors, will be involved in construction of the pre-ribosome. (Remember, this is just for the pre-ribosome.) As the complexity grows, tension increases in the orchestration:
During its transcription, the long pre-rRNA is assembled with r-proteins, ribosome biogenesis factors and small nucleolar RNAs to form a large 90S pre-ribosome. Following the first stage of pre-rRNA processing, the complex splits into two pre-ribosomes, dubbed pre-40S and pre-60S, which are eventually exported to the cytoplasm where they undergo further maturation steps and then join as 40S and 60S subunits to form the mature ribosome.
Along with the identities of the biogenesis factors came the realization that they numbered a vast 200 to 300 in eukaryotes. In the yeast Saccharomyces cerevisiae, the 90S pre-ribosome alone contains about 70 ribosome biogenesis factors -- almost as many as the number of proteins in a mature ribosome. Hence, a recurring question in the field is: why does ribosome production require so many accessory proteins?
Kornprobst’s team provided a partial answer. All these dozens of proteins are involved in multi-part complexes that work together to build the pre-ribosome.
The requirement for so many extra proteins is explained by the authors' observation that many accessory proteins are arranged around the folded pre-rRNA molecule in previously defined multi-protein complexes called UTP-A, UTP-B and UTP-C. Of these, UTP-A and UTP-B form a scaffold, within which the newly transcribed pre-rRNA is encased and so can be securely processed, modified and assembled with r-proteins.
Explained, perhaps, but not simplified! Oeffinger’s cartoon illustration of these complexes shows the pre-rRNA being threaded into a mold formed by UTP-A, UTP-B, and another factor named U3. “Encased within this mould, the pre-rRNA is safely folded and processed,” she explains. But then, we still only have the Pre-40S and Pre-60S parts of the ribosome constructed.
The role of this scaffold is reminiscent of the way in which chaperone proteins aid folding of other proteins -- a common process that prevents aggregation of proteins into non-functional structures. But although chaperone-mediated protein folding has been long established, the idea of chaperone moulds is new to RNA biology.
Keep that in mind as we talk later about the implications for the origin of life. That little U3 factor, by the way, has two functions. Half of it forms part of the scaffold. The other half is buried deep within the pre-ribosome, “presumably interacting with the pre-rRNA.” It clings to a spacer molecule that gets cleaved from the pre-rRNA. This step “is crucial for the separation of the processed 90S pre-rRNAs into pre-40S and pre-60S complexes, and the progression of ribosome production.”
We’re getting into gory details on purpose. We need to hear the complex counterpoint going on, so that the standing ovation at the end of the composition will be deserved. Remember, we are still just trying to get the “pre-ribosome” finished. Bear with us:
Kornprobst and colleagues also identified the position of the pre-18S rRNA (which will become the rRNA component of the 40S subunit) in their structure. When comparing the pre-18S structure with that of the mature 18S rRNA, the authors observed that the molecule underwent progressive folding, beginning in the domains closest to the site where transcription began. In the 90S, these regions were folded to resemble the mature 18S, whereas domains farther from the transcriptional start site were seemingly still in transitory states. This observation fits well with a previous model of hierarchical rRNA assembly.
All this and we still don’t have a working ribosome yet -- just a pre-ribosome. At this point, though, we can give hearty applause for the first movement of the symphony. Oeffinger is sure thrilled with it.
Kornprobst and colleagues have visualized in detail what, until now, has been seen through electron microscopy only as small black balls on strings of pre-rRNA. Holding a magnifying glass to the early steps of ribosome biogenesis, the authors have finally revealed a role for the multitude of ribosome biogenesis factors as a chaperone mould that provides a secure environment for the processing and folding of pre-rRNA.
The rest of the story is bound to be good. For now, we can ponder these members of a large orchestra playing together, interacting in complex sequential ways, and ask some important questions. Chiefly, could any of this have arisen by chance?
Origin-of-life researchers sometimes leap from random building blocks to a cell, or a replicator, without considering all the factors involved. They think RNA is the magic molecule that can fulfill the dual roles of metabolism and coding. Simplistic accounts, like this one on Phys.org, make it seem an “RNA World” could have preceded the DNA-protein world of life as we know it.
Actual RNA, though, is extremely delicate and nearly impossible to form in water. With copious amounts of guidance and protection by intelligent investigators in a lab, RNA can do simple things like cut itself in half or make crude copies of parts of itself. What it cannot do is code for proteins that can help it assemble. That’s putting the cart before the horse. If it needs proteins to guide and protect it into a hierarchical sequence of stages leading up to a mature ribosome, you can’t invoke raw RNA as a stepping stone for what it has to have to exist.
And no fair attributing sentience to the RNA molecules. In a sense, they’re dumb. They have no goal, and no desire to organize on a cell-making project. Some origin-of-life researchers have a bad habit of envisioning the molecules wanting to get together to form a cell. RNA starts out holding some code and metabolic function, they will say, then it “hands off” the coding to DNA and the metabolism to proteins. For a materialist, that’s cheating.
Italian biochemist Pier Luigi Luisi calls the RNA World scenario a “baseless fantasy.” See his reasons in an interview with Susan Mazur in her book The Origin of Life Circus (pp. 360-363 in particular), where he dismisses it as so unrealistic on several levels that he states that a new start is needed, a “beginner’s mind revolution” away from the RNA-DNA-centric models.
The real problem is to make ordered sequences of amino acids, and of course ordered sequences of nucleic acids – and on that the prebiotic RNA world is absolutely silent. But this view of the prebiotic RNA world is still the most popular. I think it is a case of social science psychology more than science itself (p. 363).
We do know of a cause, however, that is capable of sequencing building blocks into ordered structures. It can organize dozens of complex parts that can interact in detailed ways, in a hierarchical structure, working in sequence toward a goal. That cause (need it be said again?) is intelligence.
Intelligence is not magic. It is a cause we know and use every day. It is a cause that is necessary and sufficient for these kinds of highly ordered operations. Because of this, and because blind chance is utterly incapable of such things, intelligence is the cause that we should use in our scientific explanations.
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