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Mantle strata and CCA sequence addition
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Two Tokyo Tech professors reshape our understanding of what's happening inside our cells and beneath our feet.
The Tokyo Institute of Technology (Tokyo Tech) is justly renowned for its history of research breakthroughs in diverse fields of science. Those breakthroughs have included the discovery of ferrite and important advances in conductive polymers, in holography, and in photo-optic communications. The university's tradition of pioneering research continues apace in the physical sciences and in the life sciences. Here, two Tokyo Tech professors whose research findings have appeared in Nature in the past year discuss their recent work.
 
 

A discovery by Professor Kei Hirose, of Tokyo Tech's Department of Earth and Planetary Sciences, and his colleagues has changed our understanding of the Earth's structure. Work by Professor Osamu Nureki, of the university's Department of Biological Information, and his colleagues has provided new insight into the functioning of transfer ribonucleic acid (tRNA). Both professors have relied extensively on the power of Japan's SPring-8 synchrotron, in Hyogo Prefecture. SPring-8, the world's largest third-generation synchrotron radiation facility, provides the most powerful synchrotron radiation available on the planet.

 
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Japan's SPring-8 synchrotron facility has been a springboard for the research by Hirose and Nureki.
 

Layers and layers

Most of us tend to think of the structure of the Earth, if we think of it at all, as a three-layered affair: a hot metallic core surrounded by a vast stone mantle topped by a thin crust. Geophysicists, more sensitive to the structural subtleties beneath our feet, have identified distinct layers in the mantle. They long ago identified discontinuities in the seismic wave velocities of the mantle at depths of 410 kilometers and 660 kilometers, and researchers determined that those changes result from phase transition in the crystalline structure of the same basic material: magnesium silicate. Another, minor phase transition occurs at a depth of around 520 kilometers, but that is inside a layer generally characterized as the transition zone between the upper mantle and lower mantle.

By 1983, researchers had identified yet another discontinuity in the mantle, this one at a depth of between 2,600 kilometers and 2,700 kilometers. That's getting extremely close to the boundary—2,890 kilometers beneath the Earth's surface—between the mantle and the core. Scientists initially attributed that discontinuity to a fundamental difference in chemical composition and to a large temperature differential. But Hirose demonstrated that it, like the other discontinuities, is a phase transition. He did that by discovering a new mineral, post-perovskite.

"People had good reason to doubt that the deep-mantle discontinuity was the result of a mere phase change," observes Hirose. "The lower mantle consists mainly of magnesium silicate in a crystalline structure known as perovskite [named for the Russian mineralogist L. A. Perovski (1792–1856)]. But seismic behavior in the deepest stretches of that enigmatic realm is inconsistent with what we would expect with perovskite. Since perovskite has an extremely dense structure. a phase transition to an even-denser polymorph seemed unlikely. Seeking explanations in chemical differences was therefore only natural. The post-perovskite that we identified is denser than perovskite, however, and it appears to solve several long-standing seismic riddles."

Hirose and his colleagues made their discovery by using laser-heated diamond-anvil cell techniques. Basically, they squeeze a mineral sample between the flattened tips of two opposing diamonds in a screw-clamp fixture. With just a small screwdriver, they can produce deep-mantle pressures of more than 125 gigapascals at the 200-micron-diameter tips of the diamonds. To produce deep-mantle temperatures—around 2,500 degrees kelvin—the researchers direct a high-power laser onto the sample. They then use the powerful X-ray beam at the SPring-8 facility to analyze the resultant mineral material. Squeezing and heating the sample resulted in a material that exhibited "odd diffraction patterns," as reported in Nature.

"Chemistry professors told me there must be something wrong with my data," Hirose told Nature, "or something wrong with me." Welcome assistance arrived at that crucial juncture in the person of Professor Katsuyuki Kawamura, a mineralogist in Tokyo Tech's Department of Earth and Planetary Sciences. Hirose persuaded his colleague to have a look at the diffraction data. Kawamura determined that it contained a dense, previously unknown mineral, now known as post-perovskite, and the Earth gained a new phase transition. Subsequent work with Dr. Toshiaki Iitaka, of Japan's Institute of Physical and Chemical Research (RIKEN), revealed that the elasticity of post-perovskite explains some enigmas of the deep mantle.

 
Kei Hirose
Dr Hirose
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Hirose has achieved pressures and temperatures characteristic of the Earth's lower mantle with laser-heated diamond-anvil cell techniques. He dreams of being first to reproduce the ultrahigh pressures and temperatures that prevail at the center of the Earth. "It's a huge challenge," acknowledges Hirose, "but one well worth undertaking. Tackling that challenge successfully could unlock long-held secrets of the deepest interior of our planet."
 

Animated crystallography

Hirose's Tokyo Tech colleague Nureki has tapped the X-ray power of the SPring-8 synchrotron to analyze the dynamics of cytosine-cytosine-adenine (CCA) sequence addition and other facets of RNA functionality. He has contributed to two papers that have appeared on the pages of Nature: "Snapshots of tRNA sulfuration via an adenylated intermediate" and "Structural basis for template-independent RNA polymerization."

CCA sequence addition is a step in the translation phase of protein biosynthesis in the process of gene expression. Translation is the decoding of messenger RNA to produce a polypeptide in accordance with the genetic code. A CCA sequence at one end of a tRNA molecule is indispensable in enabling enzymes crucial to translation to recognize the tRNA. At 73 to 93 nucleotides, tRNA is a smallish variety of noncoding RNA. It transfers an amino acid to a polypeptide chain being grown at the ribosomal site of protein synthesis during translation. The CCA sequence is not native to the tRNA gene in eukaryotes and therefore needs to be added during processing. That's the sequence addition that Nureki is analyzing.

"CCA sequence addition is a tremendously exciting facet of biosynthesis," exudes Nureki. "You can only be amazed at the way the tRNA performs without the benefit of a template. It's like a factory that operates efficiently and flawlessly.

"The sequence addition is fundamental to basic life processes. Learning more about how it works could advance our understanding of those processes in lots of ways. We might be able to discover how to stop the genetic messengers, for example, when things get scripted wrong. We might learn what activates macrophages. This research also promises to shed light on how blood vessels grow. The accumulation of those kinds of basic research insights could spawn medical applications, such as means of controlling cancer progression."

A huge asset for Nureki and his colleagues has been their progress in producing animated visual records of CCA sequence addition. Other researchers had taken only still photographs—X-ray crystallographic images—of that process. Nureki and colleagues have taken photographs in series and combined them in compelling animated movies. That has engendered, he reports, a vastly improved grasp of CCA sequence addition.

 
Osamu Nureki
Dr Nureki
Blood vessels
Nureki (left) hopes that studying CCA sequence addition will improve our understanding of wide-ranging biological phenomena, such as the growth of blood vessels.
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The crystallographic animations prepared by Nureki and his colleagues are composites of actual molecular matter and computer graphics.
 
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