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Renegade RNA — Clues to cancer and normal growth
January 05, 2007Researchers at Johns Hopkins have discovered that a tiny piece of genetic code apparently goes where no bit of it has gone before, and it gets there under its own internal code.
A report on the renegade ribonucleic acid, and the code that directs its movement, will be published Jan. 5 in Science.
MicroRNAs, already implicated in cancer and normal development, latch on to and gum up larger strands of RNA that carry instructions for making the proteins that do all the cell's work. They are, says Joshua Mendell, M.D., Ph.D., an assistant professor in the McKusick-Nathans Institute of Genetic Medicine at Hopkins, like "molecular rheostats that fine-tune how much protein is being made from each gene."
That's why normally microRNAs always have appeared to stick close to the cell's protein-making machinery.
But during a survey of more than 200 of the 500 known microRNAs found in human cells, Mendell's team discovered one lone microRNA "miles away" -- in cellular terms -- from all the others.
"It was so clearly in the wrong place at the wrong time for what we thought it was supposed to be doing that we just had to figure out why," says Hun-Way Hwang, a graduate student in human genetics and contributor to the study.
Consisting of only 20 to 25 nucleotide building blocks (compared to other types of RNA that can be thousands of nucleotides long), each microRNA has a different combination of blocks. Mendell's team realized that six building blocks at the end of the wayward miR-29b microRNA were noticeably different from the ends of other microRNAs.
Suspicious that the six-block end might have something to do with miR-29b's location, the researchers chopped them off and stuck them on the end of another microRNA. When put into cells, the new microRNA behaved just like miR-29b, wandering far away from the cell's protein-making machinery and into the nucleus, where the cell's genetic material is kept.
The researchers then stuck the same six-block end onto another type of small RNA, a small-interfering RNA or siRNA that turns off genes. This also forced the siRNA into the nucleus.
According to Mendell, these results demonstrate for the first time that despite their tiny size, microRNAs contain elements consisting of short stretches of nucleotide building blocks that can control their behavior in a cell. Mendell hopes to take advantage of the built-in "cellular zip code" discovered in miR-29b as an experimental tool. For example, he plans to force other microRNAs and siRNAs into the nucleus to turn off specific sets of genes.
Mendell's team is actively hunting for additional hidden microRNA elements that control other aspects of their behavior in cells. They also are curious to figure out what miR-29b is doing in the nucleus. Because microRNAs have been implicated in cancer as well as normal development, Mendell hopes that further study of miR-29b will reveal other, hidden functions of microRNAs.
Johns Hopkins Medical Institutions
That's why normally microRNAs always have appeared to stick close to the cell's protein-making machinery.
But during a survey of more than 200 of the 500 known microRNAs found in human cells, Mendell's team discovered one lone microRNA "miles away" -- in cellular terms -- from all the others.
"It was so clearly in the wrong place at the wrong time for what we thought it was supposed to be doing that we just had to figure out why," says Hun-Way Hwang, a graduate student in human genetics and contributor to the study.
Consisting of only 20 to 25 nucleotide building blocks (compared to other types of RNA that can be thousands of nucleotides long), each microRNA has a different combination of blocks. Mendell's team realized that six building blocks at the end of the wayward miR-29b microRNA were noticeably different from the ends of other microRNAs.
Suspicious that the six-block end might have something to do with miR-29b's location, the researchers chopped them off and stuck them on the end of another microRNA. When put into cells, the new microRNA behaved just like miR-29b, wandering far away from the cell's protein-making machinery and into the nucleus, where the cell's genetic material is kept.
The researchers then stuck the same six-block end onto another type of small RNA, a small-interfering RNA or siRNA that turns off genes. This also forced the siRNA into the nucleus.
According to Mendell, these results demonstrate for the first time that despite their tiny size, microRNAs contain elements consisting of short stretches of nucleotide building blocks that can control their behavior in a cell. Mendell hopes to take advantage of the built-in "cellular zip code" discovered in miR-29b as an experimental tool. For example, he plans to force other microRNAs and siRNAs into the nucleus to turn off specific sets of genes.
Mendell's team is actively hunting for additional hidden microRNA elements that control other aspects of their behavior in cells. They also are curious to figure out what miR-29b is doing in the nucleus. Because microRNAs have been implicated in cancer as well as normal development, Mendell hopes that further study of miR-29b will reveal other, hidden functions of microRNAs.
Johns Hopkins Medical Institutions
Microrna Current Events and Microrna News RSSExperimental agent reduces breast cancer metastasis to bone
Researchers have reduced breast cancer metastasis to bone using an experimental agent to inhibit ROCK, a protein that was found to be over-expressed in metastatic breast cancer.
Study sheds light on evolution of human complexity
A painstaking analysis of thousands of genes and the proteins they encode shows that human beings are biologically complex, at least in part, because of the way humans evolved to cope with redundancies arising from duplicate genes.
MicroRNA-mediated metastasis suppression
Metastases are responsible for over 90% of cancer deaths. In the upcoming issue of G&D, Dr. Robert Weinberg (MIT) and colleagues lend molecular insight into how microRNAs suppress tumor metastasis.
Texas A&M researchers find new mechanism for circadian rhythm
Molecules that may hold the key to new ways to fight cancer and other diseases have been found to play an important role in regulating circadian rhythm, says Liheng Shi, a researcher in Texas A&M's Department of Veterinary Integrative Biosciences.
New cancer gene discovered
A new cancer gene has been discovered by a research group at the Sahlgrenska Academy. The gene causes an insidious form of glandular cancer usually in the head and neck and in women also in the breast. The discovery could lead to quicker and better diagnosis and more effective treatment.
UCSF scientists illuminate how microRNAs drive tumor progression
UCSF researchers have identified collections of tiny molecules known as microRNAs that affect distinct processes critical for the progression of cancer.
Lung cancer suppresses miR-200 to invade and spread
Primary lung cancer shifts to metastatic disease by suppressing a family of small molecules that normally locks the tumor in a noninvasive state, researchers at The University of Texas M. D. Anderson Cancer Center report in the Sept. 15 edition of Genes and Development.
Scientists Use MicroRNAs to Track Evolutionary History for First Time
The large group of segmented worms known as annelids, which includes earthworms, leeches and bristle worms, evolved millions of years ago and can be found in every corner of the world.
MicroRNAs circulating in blood show promise as biomarkers to detect pancreatic cancer
A blood test for small molecules abnormally expressed in pancreatic cancer may be a promising route to early detection of the disease.
MicroRNA in human saliva may help diagnose oral cancer
Researchers continue to add to the diagnostic alphabet of saliva by identifying the presence of at least 50 microRNAs that could aid in the detection of oral cancer, according to a report in Clinical Cancer Research, a journal of the American Association for Cancer Research.
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