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(Bio) (Chem) RNA Found in the Cellular Centrosome

 
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PostPosted: Thu Jun 08, 2006 6:47 am    Post subject: (Bio) (Chem) RNA Found in the Cellular Centrosome Reply with quote






Rensselaer Polytechnic Institute
6 June 2006

RNA found in the cellular centrosome of surf clams

TROY, N.Y. -- Researchers at Rensselaer Polytechnic Institute, the Marine Biological Laboratory (MBL) in Woods Hole and Louisiana State University (LSU) Health Sciences Center have discovered the presence of the genetic material RNA in the centrosome, the organizing structure inside each cell that assures proper cell division.
The findings, detailed June 5 in the online early edition of the journal Proceedings of the National Academy of Sciences, present evidence that individual centrosomes within a cell may carry their own genetic material.

"Our research provides direct biochemical evidence that RNA is present in the centrosomes of clam cells," says Robert Palazzo, professor of biology and director of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer.

Palazzo's laboratory isolated clam centrosomes and Mark Alliegro and Mary Anne Alliegro of LSU Health Sciences Center analyzed the centrosomes for RNA content.

"Although the possibility of DNA inside the centrosome of the cell has been ruled out by others' previous work, the presence of RNA had not been confirmed or denied until now," says Palazzo. "Our results show there are at least five specific forms of RNA in the clam cell centrosome which could be related to structure, encoding of proteins, or the regulation of organism development. The specific role or function of the RNA in the centrosome and its possible involvement in the development of animals will be significant questions in continuing studies.

"Since RNA guides the translation of genes into proteins, knowing more about its role(s) in the centrosome may help researchers better understand the progression of diseases such as cancer, which has been linked to abnormal centrosome numbers in tumor cells," says Palazzo.

The study on surf clam centrosomes was initiated at the MBL, an international biological research center where scientists use locally abundant marine organisms like surf clams and their eggs as research models. Clam eggs are modeled as simple versions of human cells, and biologists who study cell division value them for several reasons, according to Palazzo. The eggs develop fast, entering the process of cell division less than 15 minutes after fertilization, and, once fertilized, divide in synch every 30-50 minutes -- providing billions of biochemically identical cells to study.

Using a purification technique Palazzo developed at the MBL, the scientists were able to isolate relatively large quantities of clam centrosomes for their research. Palazzo collaborated with Mark Alliegro and Mary Anne Alliegro during summers at the MBL.

In addition to his position as director of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer, Palazzo also holds appointments at the MBL as visiting summer researcher and at the Wadsworth Center of the New York State Department of Health as research scientist.


###
The research was funded by the National Institute of General Medical Sciences of the National Institutes of Health.

Biotechnology and Interdisciplinary Studies at Rensselaer
At Rensselaer, faculty and students in diverse academic and research disciplines are collaborating at the intersection of the life sciences and engineering to encourage discovery and innovation. Rensselaer's four biotechnology research constellations -- biocatalysis and metabolic engineering, functional tissue engineering and regenerative medicine, biocomputation and bioinformatics, and integrative systems biology -- engage a multidisciplinary mix of faculty and students focused on the application of engineering and physical and information sciences to the life sciences. Ranked among the world's most advanced research facilities, the Center for Biotechnology and Interdisciplinary Studies at Rensselaer provides a state-of-the-art platform for collaborative research and world-class programs and symposia.

About Rensselaer
Rensselaer Polytechnic Institute, founded in 1824, is the nation's oldest technological university. The university offers bachelor's, master's and doctoral degrees in engineering, the sciences, information technology, architecture, management, and the humanities and social sciences. Institute programs serve undergraduates, graduate students and working professionals around the world. Rensselaer faculty are known for preeminence in research conducted in a wide range of fields, with particular emphasis in biotechnology, nanotechnology, information technology, and the media arts and technology. The Institute is well known for its success in the transfer of technology from the laboratory to the marketplace so that new discoveries and inventions benefit human life, protect the environment, and strengthen economic development.

*************************************************************

Questions to explore further this topic:

Cracking the Code of Life

http://www.pbs.org/wgbh/nova/genome/program_t.html

What is genetics?

http://publications.nigms.nih.gov/genetics/

What is the cell?

http://www.paete.org/forums/viewtopic.php?t=1296

What is the centrosome?

http://www.cellsalive.com/cells/centriol.htm
http://en.wikipedia.org/wiki/Centrosome
http://www.humpath.com/article.....ticle=1514
http://www.landesbioscience.co.....CC3-11.pdf

A centrosome viewed under an electron microscope

http://www.med.upenn.edu/bmcrc.....Centrosome

Cytoskeleton, microtubules and the centrosome

http://home.comcast.net/~john......leton.html

Molecular analysis of the centrosome

http://www.gurdon.cam.ac.uk/groups/raff.html
http://www.gurdon.cam.ac.uk/~b.....ovies.html

Centrosome and cancer

http://www.bcm.edu/fromthelab/.....dec_n1.htm
http://www.hbc.ku.edu/Newsltrs.....rosome.htm
http://cancerres.aacrjournals......62/14/4115

What are nucleic acids?

http://www.visionlearning.com/.....php?mid=63

What is DNA?

http://www.paete.org/forums/viewtopic.php?t=1353

What is mitosis?

http://www.johnkyrk.com/mitosis.html

What is meiosis?

http://www.johnkyrk.com/meiosis.html

Movies of centrosome fragmentation

http://www.bio.umass.edu/biolo...../anaphase/

"It Takes Two to Tango": understanding how centrosome duplication is regulated throughout the cell cycle

http://www.genesdev.org/cgi/co.....15/10/1167

What is RNA?

http://www.livescience.com/ima.....50913.html
http://www.dnaftb.org/dnaftb/21/concept/index.html
http://www.ncc.gmu.edu/dna/rna.htm
http://en.wikipedia.org/wiki/RNA
http://www.rothamsted.ac.uk/no...../rnast.htm

How is RNA made?

http://web.indstate.edu/thcme/mwking/rna.html
http://www.elmhurst.edu/~chm/v.....trans.html
http://www.ncbi.nlm.nih.gov/bo.....apter.3946

What are the different types of RNA?

tRNA
http://www.biochem.uwo.ca/meds/medna/tRNA.html

mRNA
http://www.biochem.uwo.ca/meds/medna/mRNA.html

rRNA
http://www.biochem.uwo.ca/meds/medna/rRNA.html

snRNA
http://www.biochem.uwo.ca/meds/medna/snRNA.html

What is the "RNA world"?

http://nobelprize.org/chemistr.....index.html
http://www.indigo.com/models/rna.html
http://wiki.cotch.net/index.php/RNA_world

DNA --> RNA

http://www.johnkyrk.com/DNAtranscription.html

RNA --> Protein

http://www.johnkyrk.com/DNAtranslation.html

DNA --> RNA --> Protein

http://nobelprize.org/medicine.....intro.html
http://bioinformatics.org/tutorial/1-1.html
http://www.yourgenome.org/intermediate/

Secret life of RNA

http://mednews.stanford.edu/st.....r/rna.html

How is RNA isolated?

http://www.ambion.co.jp/main/e.....ation.html
http://www.ambion.co.jp/techli.....index.html

What are surf clams?

http://www7.taosnet.com/platin.....ssurf.html
http://omp.gso.uri.edu/discove.....surfcm.htm
http://www.csc.noaa.gov/lcr/ny.....pisul.html

GAMES

http://www.pbs.org/wgbh/nova/genome/sequencer.html
http://www.pbs.org/wgbh/nova/israel/family.html
http://anthro.palomar.edu/mend.....sword.html
http://genetics.gsk.com/kids/dna01.htm
http://genetics.gsk.com/kids/heredity01.htm
http://www.koshlandsciencemuse.....-gd002.jsp
http://www.agameaday.com/066/066calendar1.htm


Last edited by adedios on Sat Jan 27, 2007 4:07 pm; edited 2 times in total
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PostPosted: Fri Jun 09, 2006 1:21 pm    Post subject: How Life Began: New Research Suggests Simple Approach Reply with quote

How Life Began: New Research Suggests Simple Approach

By Michael Schirber
Special to LiveScience
posted: 09 June 2006
09:09 am ET



Somewhere on Earth, close to 4 billion years ago, a set of molecular reactions flipped a switch and became life. Scientists try to imagine this animating event by simplifying the processes that characterize living things.

New research suggests the simplification needs to go further.


For the full article:

http://www.livescience.com/ani.....rigin.html
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PostPosted: Tue Aug 22, 2006 11:24 am    Post subject: Rehydrate -- your RNA needs it Reply with quote

University of Michigan
22 August 2006

Rehydrate -- your RNA needs it

ANN ARBOR, Mich.---Water, that molecule-of-all-trades, is famous for its roles in shaping the Earth, sustaining living creatures and serving as a universal solvent.

Now, researchers at the University of Michigan and the Academy of Sciences of the Czech Republic have uncovered two previously unknown roles for water in RNA enzymes, molecules which themselves play critical roles in living cells and show promising medical applications.

The researchers' findings will be published online in the Proceedings of the National Academy of Sciences (PNAS) this week.

RNA enzymes, also known as ribozymes, accelerate chemical reactions inside cells, just as their better-known protein counterparts do. And just as a protein enzyme is not a static structure, a ribozyme also changes shape, cycling back and forth between active and inactive forms (called conformations).

In earlier work, a team led by U-M's Nils Walter, associate professor of chemistry, found that modifications made anywhere on the ribozyme molecule---even far from the site where the chemical reaction occurs---affect the rates at which the enzyme changes conformation and catalyzes the reaction. Something similar had been seen in protein enzymes, but never before in RNA enzymes.

The earlier finding, published in PNAS two years ago, suggested that information about changes in distant parts of the ribozyme travels through some sort of network to the core of the molecule, where chemical reactions take place. The latest work shows that water molecules trapped inside the ribozyme's core are essential components of that network.

The network acts like a jostling crowd at a cocktail party, where hydrogen bonds---weak, electrostatic attractions between molecules or parts of molecules---take the place of handshakes. Water molecules trapped in ribozymes can form hydrogen bonds with other water molecules or with parts of the ribozyme molecule.

"The way we interpret the data is that in ribozymes, a chemical modification introduced at one place changes the local structure slightly," Walter said. The building blocks making up the ribozyme wiggle into different positions and in the process must let go of some hydrogen bonds and form others, just as partygoers shift position and engage with other guests.

"As a consequence, their hydrogen bonding partners---some of which are water molecules---also rearrange. Then their hydrogen bonding partners also rearrange, creating a domino effect, where a local modification spreads throughout the molecule and modifies the structure elsewhere, even at quite a distance," Walter said. Water facilitates the process by increasing the number of hydrogen bonds and making the ribozyme behave as an interconnected whole.

Walter and coworkers also found evidence that water is directly involved in catalyzing reactions in the ribozyme's core, another previously unknown role. The research team explored the new roles of water molecules using a combination of computational simulations and a technique called single-molecule fluorescence resonance energy transfer (FRET), which allowed the researchers to directly observe and measure how quickly the ribozyme switched forms and how the rates changed when various parts of the molecule were altered.

The situation in ribozymes contrasts with what happens in protein enzymes, which repel water from their cores and rely on direct contact, rather than a network of hydrogen bonds, to communicate structural changes from one part of the molecule to another.

So far, the researchers have focused on one particular ribozyme, but Walter predicts the findings will apply to other RNAs. If so, those findings should be of great interest to scientists who are learning more all the time about the diverse roles of RNA. Once thought to be only a passive carrier of encoded genetic information, RNA is now known to regulate gene expression and other important cellular processes and to act as a sort of sensor---detecting cellular signals and carrying out appropriate reactions in response. In fact, there are many more so-called non-protein coding RNAs in the cell (around 100,000 in humans), which are not translated into protein, than there are protein coding messenger RNAs (about 25,000), making these vast numbers of RNA molecules central players in our bodies.

Work is also underway in academic and industrial labs around the world to engineer RNA for medical purposes. The engineered molecules, called RNA aptamers, are selected for their ability to bind to particular proteins involved in certain diseases, blocking key steps in the disease process.

"It's likely that water helps mediate the binding between these aptamers and their disease-causing protein targets, ultimately keeping the protein away from where it can wreak havoc," Walter said. "So the fundamental understanding we are gaining of the role of water in RNA almost certainly will have relevance in the treatment or prevention of disease."


###
For more information on Walter, visit: http://www.umich.edu/~michchem/faculty/walter/

News release on earlier, related research: http://www.umich.edu/news/inde.....04/r062904

RNA enzymes: http://www.umich.edu/~rnapeopl/Walter(02b).pdf

Proceedings of the National Academy of Sciences: http://www.pnas.org/
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PostPosted: Tue Dec 05, 2006 9:42 am    Post subject: Peering into the shadow world of RNA Reply with quote

The Wistar Institute
5 December 2006

Peering into the shadow world of RNA

Crosstalk between different forms of non-coding RNA may control the genome
(PHILADELPHIA) -- The popular view is that DNA and genes control everything of importance in biology. The genome rules all of life, it is thought.

Increasingly, however, scientists are realizing that among the diverse forms of RNA, a kind of mirror molecule derived from DNA, many interact with each other and with genes directly to manage the genome from behind the scenes.

In particular, RNA produced by the vast stretches of DNA that do not code for any genes – long considered “junk” DNA – may in fact be serving vital duty by governing important aspects of gene expression. This type of RNA is called non-coding RNA, meaning that although it may be biologically active, it does not carry the instructions for producing any protein in the body.

The importance of better understanding these non-coding forms of RNA is underscored by the fact that they are known to play roles in such critical processes as embryonic development, cell and tissue differentiation, and cancer formation.

A review of current research in this still-developing area of biology, authored by Kazuko Nishikura, Ph.D., a professor in the Gene Expression and Regulation Program at The Wistar Institute, appears in the December issue of the journal Nature Reviews Molecular Cell Biology (http://www.nature.com/nrm/journal/v7/n12/full/nrm2061.html).

“The essence of gene regulation occurs, of course, at the level of gene transcription,” Nishikura says. “Cellular machinery transcribes genetic DNA into messenger RNA from which the proteins of the body are produced. In the last several years, however, scientists investigating the biological meaning of other forms of RNA that don’t code for proteins have discovered that they oversee another, more subtle level of genome control.”

Nishikura’s own research has for many years explored RNA editing mechanisms. In particular, she has studied an enzyme called ADAR that converts specific occurrences of a basic RNA building-block molecule called adenosine into another called inosine. In her laboratory, this simple substitution has been seen to have significant biological effects, altering the expression of certain neurotransmitter genes, for example.

Last year, this work converged with that of researchers investigating an extensive family of small molecules called microRNAs, or miRNAs, non-coding forms of RNA that appear to target and inactivate particular sets of messenger RNAs, thus preventing them from producing protein and effectively silencing the group of genes from which they were transcribed. In that study, Nishikura found that that precursor miRNAs, like messenger RNAs, are themselves subject to specific RNA editing, the result of which is to suppress – or perhaps refocus – miRNA expression and activity (http://www.nature.com/nsmb/journal/v13/n1/full/nsmb1041.html).

“MicroRNAs often target a specific set of genes,” Nishikura notes. “But when editing occurs, they may target a completely different set of genes.”

In recent years, Nishikura says, a growing number of scientists are discovering other links between RNA editing and the activities of different forms of non-coding RNA.

“We used to believe there were only a limited number of RNA editing sites,” she says, “but now we think there may be as many as 20,000 sites involving perhaps 3,000 genes. Interestingly, most of the editing sites correlate with non-coding regions of DNA, the so-called junk DNA.”

One reason for this, Nishikura and others speculate, may be that the majority of these non-coding regions are composed of repetitive sequences of DNA called transposons. The largest class of transposons, known as retrotransposons, have the remarkable ability to copy themselves into RNA, translate themselves back into DNA, and then reinsert themselves back into the DNA at the new location. If their insertion spot happens to be within the coding region for a vital gene, the result can be destruction of the gene, leading to birth defects and genetic disease.

Over evolutionary history, this ability of transposons to copy themselves to new locations has helped them to dramatically expand their representation in the mammalian genome.

“Transposons occupy as much as half of our entire genome, and they can be dangerous,” Nishikura says. “As a result, mechanisms have arisen through evolution to suppress their activity. This is particularly true in the egg and sperm, where maintenance of the genome’s integrity is critical.”

One of these suppression mechanisms involves short interfering RNA, or siRNA, a form of non-coding RNA that specifically targets and inactivates the stretch of DNA from which it originated. In the case of transposons, this would effectively limit their ability to act, thus protecting the genome from potential disruption.

###
Research in the Nishikura laboratory is supported in part by grants from the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the Commonwealth Universal Research Enhancement Program of the Pennsylvania Department of Health.

The Wistar Institute is an international leader in biomedical research, with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. Discoveries at Wistar have led to the creation of the rubella vaccine that eradicated the disease in the U.S., rabies vaccines used worldwide, and a new rotavirus vaccine approved in 2006. Wistar scientists have also identified many cancer genes and developed monoclonal antibodies and other important research tools. Today, Wistar is home to eminent melanoma researchers and pioneering scientists working on experimental vaccines against flu, HIV, and other diseases. The Institute works actively to transfer its inventions to the commercial sector to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today’s Discoveries – Tomorrow’s Cures. On the web at www.wistar.org.
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PostPosted: Mon Jan 15, 2007 11:01 am    Post subject: Closing a loophole in the RNA World Hypothesis Reply with quote

Closing a loophole in the RNA World Hypothesis
Journal of the American Chemical Society
15 January 2007

New scientific research may close a major loophole in the RNA world hypothesis, the idea that ribonucleic acid -- not the fabled DNA that makes up genes in people and other animals -- was the key to life's emergence on Earth 4.6 billion years ago. That hypothesis states that RNA catalyzed all the biochemical reactions necessary to produce living organisms. Only later were those self-replicating RNA units joined by organisms based on DNA, which evolved into more advanced forms of life.

But how did ribonucleic acid appear? Scientists have shown that other organic compounds can form spontaneously under conditions believed to exist on the primordial Earth. The University of Manchester's John D. Sutherland and colleagues point out, however, that no plausible prebiotic synthesis of ribonucleotides, the components of RNA, has been reported. His group offers the large part of such a potential synthesis in an article scheduled for the Jan. 17 issue of the Journal of the American Chemical Society, a weekly publication.

The researchers describe a process in which each of the two components for a ribonucleotide form in different locations on the primordial Earth. They combine when one evaporates and is delivered to the location of the second component in rainfall.

ARTICLE #2 FOR IMMEDIATE RELEASE
"Two-Step Potentially Prebiotic Synthesis of alpha-D-Cytidine-5'-phosphate from D-Gylceraldehyde-3-phosphate"

DOWNLOAD PDF
http://pubs.acs.org/cgi-bin/sa.....66495v.pdf

DOWNLOAD HTML
http://pubs.acs.org/cgi-bin/sa.....6495v.html

CONTACT:
John D. Sutherland, Ph.D.
The University of Manchester
Manchester, UK
Phone: +44-161-275-4614
Fax: +44-161-275-4598
Email: john.sutherland@manchester.ac.uk
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PostPosted: Fri Mar 16, 2007 8:22 am    Post subject: RNA enzyme structure offers a glimpse into the origins of li Reply with quote

University of California - Santa Cruz
15 March 2007

RNA enzyme structure offers a glimpse into the origins of life

SANTA CRUZ, CA -- Researchers at the University of California, Santa Cruz, have determined the three-dimensional structure of an RNA enzyme, or "ribozyme," that carries out a fundamental reaction required to make new RNA molecules. Their results provide insight into what may have been the first self-replicating molecule to arise billions of years ago on the evolutionary path toward the emergence of life.

In all forms of life known today, the synthesis of DNA and RNA molecules is carried out by enzymes made of proteins. The instructions for making those proteins are contained in genes made of DNA or RNA (nucleic acids). The circularity of this process poses a challenge for theories about the origins of life.

"Which came first, nucleic acids or proteins? This question once seemed an intractable paradox, but with the discovery of ribozymes, it is now possible to imagine a prebiotic 'RNA World' in which self-replicating ribozymes accomplished both tasks," said William Scott, associate professor of chemistry and biochemistry at UC Santa Cruz.

Scott and postdoctoral researcher Michael Robertson determined the structure of a ribozyme that joins two RNA subunits together in the same reaction that is carried out in biological systems by the protein known as RNA polymerase. Their findings are published in the March 16 issue of the journal Science.

"An RNA-dependent RNA polymerase ribozyme is the foundation of the entire RNA World hypothesis," Robertson said. "With that, you would have an RNA capable of making copies of itself; mutations or errors in some copies would result in variations that would be acted on by Darwinian natural selection, and the molecules would evolve into bigger and better ribozymes. That's what makes this structure so interesting."

Robertson and Scott determined the structure of a ribozyme that is not an entirely self-replicating RNA molecule, but it does carry out the fundamental reaction required of such a molecule--a "ligase" reaction creating a bond between two RNA subunits.

Robertson obtained the ligase ribozyme through a kind of test-tube evolution when he was a graduate student at the University of Texas, Austin, working in the lab of biochemist Andrew Ellington. Starting with a mixture of randomly synthesized RNA molecules and selecting for the desired properties, researchers are able to evolve RNA enzymes from scratch. In the Ellington lab, Robertson evolved the ligase ribozyme (called the L1 ligase) and determined which parts were critical for its function and which parts could be removed to create a "minimal construct."

At UC Santa Cruz, he began trying to grow crystals of the ribozyme so that he could use x-ray crystallography to determine its structure. Crystallizing RNA molecules is extremely difficult, and Robertson tried dozens of different versions of the ribozyme under different conditions before he succeeded. Using x-ray crystallography--which involves shining a beam of x-rays through the crystals and analyzing the resulting diffraction patterns--Robertson and Scott were then able to determine the three-dimensional structure of the ribozyme.

The ribozyme has three stems that radiate from a central hub. The active site where ligation occurs is located on one stem, and the structure shows that the molecule folds in such a way that parts of another stem are positioned over the ligation site, forming a pocket where the reaction takes place. A magnesium ion bound to one stem and positioned in the pocket plays an important role in the reaction, Robertson said.

The structure indicates that this artificially selected ribozyme uses reaction mechanisms that are much like those used by naturally occuring enzymes, Robertson said.

"The L1 ligase appears to use strategies of transition-state stabilization and acid-base catalysis similar to those that exist for natural ribozymes and protein enzymes," he said.
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PostPosted: Fri Jan 04, 2008 2:22 pm    Post subject: New route for heredity bypasses DNA Reply with quote

New route for heredity bypasses DNA
by Nancy Forbes
January 4, 2008

A group of scientists in Princeton's Department of Ecology and Evolutionary Biology has uncovered a new biological mechanism that could provide a clearer window into a cell's inner workings.

What's more, this mechanism could represent an "epigenetic" pathway -- a route that bypasses an organism's normal DNA genetic program -- for so-called Lamarckian evolution, enabling an organism to pass on to its offspring characteristics acquired during its lifetime to improve their chances for survival. Lamarckian evolution is the notion, for example, that the giraffe's long neck evolved by its continually stretching higher and higher in order to munch on the more plentiful top tree leaves and gain a better shot at surviving.

The research also could have implications as a new method for controlling cellular processes, such as the splicing order of DNA segments, and increasing the understanding of natural cellular regulatory processes, such as which segments of DNA are retained versus lost during development. The team's findings will be published Jan. 10 in the journal Nature.

Princeton biologists Laura Landweber, Mariusz Nowacki and Vikram Vijayan, together with other members of the lab, wanted to decipher how the cell accomplished this feat, which required reorganizing its genome without resorting to its original genetic program. They chose the singled-celled ciliate Oxytricha trifallax as their testbed.

Ciliates are pond-dwelling protozoa that are ideal model systems for studying epigenetic phenomena. While typical human cells each have one nucleus, serving as the control center for the cell, these ciliate cells have two. One, the somatic nucleus, contains the DNA needed to carry out all the non-reproductive functions of the cell, such as metabolism. The second, the germline nucleus, like humans' sperm and egg, is home to the DNA needed for sexual reproduction.

When two of these ciliate cells mate, the somatic nucleus gets destroyed, and must somehow be reconstituted in their offspring in order for them to survive. The germline nucleus contains abundant DNA, yet 95 percent of it is thrown away during regeneration of a new somatic nucleus, in a process that compresses a pretty big genome (one-third the size of the human genome) into a tiny fraction of the space. This leaves only 5 percent of the organism's DNA free for encoding functions. Yet this small hodgepodge of remaining DNA always gets correctly chosen and then descrambled by the cell to form a new, working genome in a process (described as "genome acrobatics") that is still not well understood, but extremely deliberate and precise.

Landweber and her colleagues have postulated that this programmed rearrangement of DNA fragments is guided by an existing "cache" of information in the form of a DNA or RNA template derived from the parent's nucleus. In the computer realm, a cache is a temporary storage site for frequently used information to enable quick and easy access, rather than having to re-fetch or re-create the original information from scratch every time it's needed.

"The notion of an RNA cache has been around for a while, as the idea of solving a jigsaw puzzle by peeking at the cover of the box is always tempting," said Landweber, associate professor of ecology and evolutionary biology. "These cells have a genomic puzzle to solve that involves gathering little pieces of DNA and putting them back together in a specified order. The original idea of an RNA cache emerged in a study of plants, rather than protozoan cells, though, but the situation in plants turned out to be incorrect."

Through a series of experiments, the group tested out their hypothesis that DNA or RNA molecules were providing the missing instruction booklet needed during development, and also tried to determine if the putative template was made of RNA or DNA. DNA is the genetic material of most organisms, however RNA is now known to play a diversity of important roles as well. RNA is DNA's chemical cousin, and has a primary role in interpreting the genetic code during the construction of proteins.

First, the researchers attempted to determine if the RNA cache idea was valid by directing specific RNA-destroying chemicals, known as RNAi, to the cell before fertilization. This gave encouraging results, disrupting the process of development, and even halting DNA rearrangement in some cases.

In a second experiment, Nowacki and Yi Zhou, both postdoctoral fellows, discovered that RNA templates did indeed exist early on in the cellular developmental process, and were just long-lived enough to lay out a pattern for reconstructing their main nucleus. This was soon followed by a third experiment that "… required real chutzpah," Landweber said, "because it meant reprogramming the cell to shuffle its own genetic material."

Nowacki, Zhou and Vijayan, a 2007 Princeton graduate in electrical engineering, constructed both artificial RNA and DNA templates that encoded a novel, pre-determined pattern; that is, that would take a DNA molecule of the ciliate's consisting of, for example, pieces 1-2-3-4-5 and transpose two of the segments, to produce the fragment 1-2-3-5-4. Injecting their synthetic templates into the developing cell produced the anticipated results, showing that a specified RNA template could provide a new set of rules for unscrambling the nuclear fragments in such a way as to reconstitute a working nucleus.

"This wonderful discovery showed for the first time that RNA can provide sequence information that guides accurate recombination of DNA, leading to reconstruction of genes and a genome that are necessary for the organism," said Meng-Chao Yao, director of the Institute of Molecular Biology at Taiwan's Academia Sinica. "It reveals that genetic information can be passed on to following generations via RNA, in addition to DNA."

The research team believes that if this mechanism extends to mammalian cells, then it could suggest novel ways for manipulating genes, besides those already known through the standard methods of genetic engineering. This could lead to possible applications for creating new gene combinations or restoring aberrant cells to their original, healthy state.

Support for the team's research was provided by the National Science Foundation, the National Institutes of Health and the School of Engineering and Applied Science senior thesis research fund.
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