 |
|
Protein splicing upsets the DNA colinearity paradigm
September 08, 2006Novel mechanism of protein processing found
Understanding medical research problems often relies on the direct, linear relationship between the sequence of a protein and the DNA encoding that protein. In fact, colinearity of DNA and protein sequences is thought to be a fundamental feature of the universal genetic code. However, a paper published today in Science by a team from the Brussels Branch of the global Ludwig Institute for Cancer Research (LICR) and the Seattle-based Fred Hutchinson Cancer Research Center (FHCRC), shows that a protein can be rearranged so that it is no longer colinear with its encoding DNA.
Genes have stretches of (protein) coding DNA sequences interspersed with stretches of non-coding DNA sequences. The first step in making the protein is the faithful transcription of the entire gene's sequence into an RNA sequence. The RNA is then 'spliced' such that the non-coding sequences are removed and the coding sequences are assembled in a linear fashion to form the template for translation from RNA to protein.
"Until now it was thought that colinearity of DNA and protein sequences was only interrupted by RNA splicing," says LICR's Dr. Benoit Van den Eynde, the study's senior author. "This new study shows that protein splicing also occurs, and may even result in protein fragments, or peptides, being spliced together in the order opposite to that which occurs in the parental protein."
According to Dr. Van den Eynde, this novel phenomenon occurs during the physiological function of 'antigen processing,' which produces antigenic peptides; the 'red flags' that mark cells for destruction by the immune system.
The immune system attacks 'foreign' cells-be they tumor cells, virally infected, or donated by another person-when T lymphocytes recognize antigenic peptides displayed on the cell surface. The antigens are created by 'proteasomes,' components of the cell machinery that cut foreign proteins into peptides that are then displayed on the cell surface for recognition and destruction by CD8+ T lymphocytes. However, the Belgium/USA team has found that proteasomes can also splice the peptide fragments together in a reverse order to that encoded by the protein's DNA sequence template. This takes the possible number of antigens from any one protein into potentially thousands of sequence configurations.
The sequence of the first human cancer-specific antigen, which was identified at the LICR Brussels Branch, has allowed the development of antigen-specific cancer vaccines that are in clinical trials around the world. This study describes a mechanism that significantly extends the number of antigenic peptides that can be produced from a single protein, and therefore widens the applicability of peptide vaccines against cancer and infectious diseases.
Ludwig Institute for Cancer Research
"Until now it was thought that colinearity of DNA and protein sequences was only interrupted by RNA splicing," says LICR's Dr. Benoit Van den Eynde, the study's senior author. "This new study shows that protein splicing also occurs, and may even result in protein fragments, or peptides, being spliced together in the order opposite to that which occurs in the parental protein."
According to Dr. Van den Eynde, this novel phenomenon occurs during the physiological function of 'antigen processing,' which produces antigenic peptides; the 'red flags' that mark cells for destruction by the immune system.
The immune system attacks 'foreign' cells-be they tumor cells, virally infected, or donated by another person-when T lymphocytes recognize antigenic peptides displayed on the cell surface. The antigens are created by 'proteasomes,' components of the cell machinery that cut foreign proteins into peptides that are then displayed on the cell surface for recognition and destruction by CD8+ T lymphocytes. However, the Belgium/USA team has found that proteasomes can also splice the peptide fragments together in a reverse order to that encoded by the protein's DNA sequence template. This takes the possible number of antigens from any one protein into potentially thousands of sequence configurations.
The sequence of the first human cancer-specific antigen, which was identified at the LICR Brussels Branch, has allowed the development of antigen-specific cancer vaccines that are in clinical trials around the world. This study describes a mechanism that significantly extends the number of antigenic peptides that can be produced from a single protein, and therefore widens the applicability of peptide vaccines against cancer and infectious diseases.
Ludwig Institute for Cancer Research
Dna Current Events and Dna News RSSInsect Resistance to Bt Crops can be Predicted, Monitored, and Managed
Since 1996, crop plants genetically modified to produce bacterial proteins that are toxic to certain insects, yet safe for people, have been planted on more than 200 million hectares worldwide.
Possible Link Studied Between Childhood Abuse and Early Cellular Aging
Children who suffer physical or emotional abuse may be faced with accelerated cellular aging as adults, according to new research from Butler Hospital and Brown University.
Biologists discover bacterial defense mechanism against aggressive oxygen
Bacteria possess an ingenious mechanism for preventing oxygen from harming the building blocks of the cell.
Just like old times: Generating RNA molecules in water
A key question in the origin of biological molecules like RNA and DNA is how they first came together billions of years ago from simple precursors.
Gene mismatch influences success of bone marrow transplants
A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics.
Scientists at UA, collaborating institutions decode maize genome
Scientists from the University of Arizona led by Arizona Genomics Institute director Rod A. Wing and from collaborating institutions have deciphered the complete genetic code of the maize plant for the first time.
Ancestry attracts, but love is blind
People preferentially marry those with similar ancestry, but their decisions are not necessarily based on hair, eye or skin colour.
Scientists unlock clues for tailoring corn plant for food, energy needs
Scientists have long known that the offspring of two inbred strains tend to be superior to both their parents. Now, a team of researchers including a University of Florida geneticist has discovered clues to why that might be the case for one of the most important crops in the world: corn.
Cigarettes Harbor Many Bacteria Harmful to Human Health
Cigarettes are "widely contaminated" with bacteria, including some known to cause disease in people, concludes a new international study conducted by a University of Maryland environmental health researcher and microbial ecologists at the Ecole Centrale de Lyon in France.
Technique finds gene regulatory sites without knowledge of regulators
A new statistical technique developed by researchers at the University of Illinois allows scientists to scan a genome for specific gene-regulatory regions without requiring prior knowledge of the relevant transcription factors.
More Dna Current Events and Dna News Articles
 |
Thames & Kosmos Genetics and DNA by Thames & Kosmos In depth investigation of genetics and DNA. Isolate the DNA from a tomato, learn about inheritance and how traits are expressed, build a DNA model, breed bacteria to experiment with genetic engineering. The full-color, 48-page manual guides your experiments. |
 |
DNA: The Secret of Life by James D. Watson (Author) James Watson, the co-discoverer of the structure of DNA and author of the international bestseller "The Double Helix" tells the story of the amazing molecule since its discovery fifty years ago, following modern genetics from his own Nobel prize-winning work in the fifties to today's Dolly the sheep, designer babies and GM foods. Professor Watson introduces the science of modern genetics, along with its history and its implications, in this magnificent guide to one of the most triumphant achievements of human science. |
 |
Science Wiz DNA Kit by Sciencewiz The central concepts of molecular biology becomes child's play in this set of camp favorites. 40 Page science book and materials with 8 Major Activities. Makes the DNA revolution accessible. Extract DNA from a fruit Probe and spool real DNA Build a double helix Solve a chromosome puzzle Is it a boy or a girl? Play the gene construction game Country of Origin: U.S.A., China & Hong Kong. |
 |
DNA Science: A First Course, Second Edition by David Micklos (Author), Greg A. Freyer (Author) This is the second edition of a highly successful textbook (over 50,000 copies sold) in which a highly illustrated, narrative text is combined with easy–to–use thoroughly reliable laboratory protocols. It contains a fully up–to–date collection of 12 rigorously tested and reliable lab experiments in molecular biology, developed at the internationally renowned Dolan DNA Learning Center of Cold Spring Harbor Laboratory, which culminate in the construction and cloning of a recombinant DNA molecule. Proven through more than 10 years’ of teaching at research and nonresearch colleges and universities, junior colleges, community colleges, and advanced biology programs in high school, this book has been successfully integrated into introductory biology, general biology,... |
 |
K'NEX Educational DNA, Replications and Transcription Set by K'NEX K'Nex kits inspire young minds and satisfy kids' curiosity on how to build simple creations. Each innovative kit keeps young builders busy and intrigued for hours on end. This K'Nex Kit allows one to two kids to work as a team. Models demonstrate the structure and processes of DNA and mRNA molecules. Everything comes in a large compartmentalized storage case with snap-on lid. Curriculum sold separately. |
 |
Genes and DNA (Kingfisher Knowledge) by Richard Walker (Author), Steve Jones (Author) Genes & DNA explores modern genetics, from an investigation of genes and their function, to forensics, therapy, and cloning. |
 |
DNA on DNA by DNA Previously released on CD by No More Records, now issued on a limited edition 2LP featuring newly-discovered songs exclusive to this LP: "Pompeii," "Shrinking Thing," "Drinking Water," plus two encores from DNA's final performance at CBGB's. Definitive collection of studio and live recordings by New York's seminal no wave band DNA. Surviving two line-ups over a brief period of four years; this highly influential, strikingly original and extremely under-recorded band left a huge void in its wake. Formed in 1978, Brazilian-raised singer/guitarist Arto Lindsay hastily assembled an international trio of non-musicians. Robin Crutchfield played keyboard and Japan's Ikue Mori played drums. DNA played their first gig within weeks and recorded their first 7" shortly afterwards. The ear of Brian... |
 |
DNA Starring: Tom Conti Also With: Samantha Bond (Performer) Forensics expert Joe Donovan uses science to snare killers—and save himself. Award-winning actor Tom Conti (Shirley Valentine; Reuben, Reuben) stars as Joe Donovan, an accomplished but troubled criminologist who returns from a mental breakdown to lead Manchester’s crack Forensic Investigations Unit. Called in to consult on a murder case that suspiciously resembles the one that drove him into near madness years ago, Donovan redeems his reputation and rediscovers his devotion to the job. Yet his professional dedication bleeds into his personal life, alienating his wife (Samantha Bond, Die Another Day, Tomorrow Never Dies) but appealing to his son (Ryan Cartwright, The Grimleys), who wants to follow in his father’s footsteps. Packed with fascinating procedural details and... |
 |
The Stuff of Life: A Graphic Guide to Genetics and DNA by Mark Schultz (Author), Zander Cannon (Illustrator), Kevin Cannon (Illustrator) The Stuff of Life gives readers a complete introduction to the history of genetics that's as easy to understand as it is entertaining to read. |
 |
Discovery Exclusive DNA Explorer Kit by DISCOVERY CHANNEL Explore one of the newest frontiers in science - DNA mapping. From science labs to courtrooms, few discoveries are as exciting as the world of DNA. With this deluxe, first-of-its-kind kit, you can extract, view and map real DNA yourself. Ideal for budding forensic-scientists or secret agents, the working lab and tools are just like the real thing. Plus, you |
| © 2009 BrightSurf.com |