|
New plant study reveals a 'deeply hidden' layer of the transcriptome
December 28, 2007La Jolla, CA - Cells keep a close watch over the transcriptome - the totality of all parts of the genome that are expressed in any given cell at any given time. Researchers at the Salk Institute for Biological Studies and the University of Missouri-Kansas City teamed up to peel back another layer of transcriptional regulation and gain new insight into how genomes work.
Converting the "genetic blueprint" into molecular building blocks requires two basic processes: transcription, which copies the information from DNA into RNA transcripts and takes place in the cell's nucleus, and translation, where the RNA serves as a template to manufacture proteins outside the nucleus.
But before transcripts can guide protein synthesis or take on regulatory functions, they have to undergo a strict mRNA surveillance system that degrades defective, obsolete, and surplus transcripts. In their study, published in the Dec. 28 issue of Cell, the scientists zoomed in on a specific subclass of transcripts that are under the control of the exosome, a molecular machine in charge of controlled RNA degradation.
"We found evidence for widespread exosome-mediated RNA quality control in plants and a 'deeply hidden' layer of the transcriptome that is tightly regulated by exosome activity," says Joseph R. Ecker, Ph.D., professor in the Plant Biology Laboratory and director of the Salk Institute Genomic Analysis Laboratory.
Since the exosome is in the business of chewing things up, the scientists inactivated the multi-unit complex to bring its otherwise invisible substrates to the fore. Then they combed the transcriptional landscape for hitherto unseen peaks of transcripts that now were untouched by the degrading force of the exosome complex and came up with a genome-wide atlas of Arabidopsis exosome targets.
"Our careful design and rigorous validation of the system for conditionally and quickly inactivating the exosome turned out to be really crucial for homing in on its RNA targets," explains Dmitry A. Belostotsky of the University of Missouri-Kansas City. "On the other hand, genome-wide analyses of permanent genetic mutations often produce a complex mixture of direct and indirect effects, making it very hard to untangle. Thus, we think our strategy has a broadly-applicable value."
"From a genomics perspective it really allowed us to visualize what information from the genome is actually expressed," adds co-first author Brian D. Gregory, Ph.D., a postdoctoral researcher in Ecker's lab. "When you knock down exosome activity, you see changes in the transcriptome that are not visible under any other circumstance."
Since the common notion is that the exosome plays a central role in bulk RNA turnover, the researchers say, they expected to find the levels of all transcripts increasing when they inactivated the exosome complex. "But not everything is going up, instead the exosome mechanism seems to be very tightly regulated," says Ecker. "We didn't see regions that are known to be silenced to go up, instead we found a very specific group of transcripts that are regulated in this way."
Among them are regular protein-coding RNAs, RNA processing intermediates and hundreds of non-coding RNAs, the vast majority of which hadn't been described before. "These strange transcripts are associated with small RNA-producing loci as well as with repetitive sequence elements," says Gregory. "They are under very tight regulation by the exosome, but we still don't know exactly what this means."
"It is likely that these RNAs that are usually 'deeply hidden' become important for genome function or stability under some circumstances", adds co-first author Julia Chekanova, an assistant at the University of Missouri-Kansas City. "We need to do more work to figure out what these circumstances are."
Salk Institute
"We found evidence for widespread exosome-mediated RNA quality control in plants and a 'deeply hidden' layer of the transcriptome that is tightly regulated by exosome activity," says Joseph R. Ecker, Ph.D., professor in the Plant Biology Laboratory and director of the Salk Institute Genomic Analysis Laboratory.
Since the exosome is in the business of chewing things up, the scientists inactivated the multi-unit complex to bring its otherwise invisible substrates to the fore. Then they combed the transcriptional landscape for hitherto unseen peaks of transcripts that now were untouched by the degrading force of the exosome complex and came up with a genome-wide atlas of Arabidopsis exosome targets.
"Our careful design and rigorous validation of the system for conditionally and quickly inactivating the exosome turned out to be really crucial for homing in on its RNA targets," explains Dmitry A. Belostotsky of the University of Missouri-Kansas City. "On the other hand, genome-wide analyses of permanent genetic mutations often produce a complex mixture of direct and indirect effects, making it very hard to untangle. Thus, we think our strategy has a broadly-applicable value."
"From a genomics perspective it really allowed us to visualize what information from the genome is actually expressed," adds co-first author Brian D. Gregory, Ph.D., a postdoctoral researcher in Ecker's lab. "When you knock down exosome activity, you see changes in the transcriptome that are not visible under any other circumstance."
Since the common notion is that the exosome plays a central role in bulk RNA turnover, the researchers say, they expected to find the levels of all transcripts increasing when they inactivated the exosome complex. "But not everything is going up, instead the exosome mechanism seems to be very tightly regulated," says Ecker. "We didn't see regions that are known to be silenced to go up, instead we found a very specific group of transcripts that are regulated in this way."
Among them are regular protein-coding RNAs, RNA processing intermediates and hundreds of non-coding RNAs, the vast majority of which hadn't been described before. "These strange transcripts are associated with small RNA-producing loci as well as with repetitive sequence elements," says Gregory. "They are under very tight regulation by the exosome, but we still don't know exactly what this means."
"It is likely that these RNAs that are usually 'deeply hidden' become important for genome function or stability under some circumstances", adds co-first author Julia Chekanova, an assistant at the University of Missouri-Kansas City. "We need to do more work to figure out what these circumstances are."
Salk Institute
Transcriptome News and Current Transcriptome Events RSSSalivary diagnostics, the 'magic mirror' to your health ... at your personal computer
Accuracy, convenience, and non-invasiveness are the most critical characteristics for any diagnostic tool. A new concept, Salivaomics Knowledge Base (SKB), an in silico (i.e., performed on computer or via computer simulation) saliva diagnostic atlas, is launching today during the 37th Annual Meeting of the American Association for Dental Research in Dallas, Texas.
Scientists use saliva's 'diagnostic alphabets' to diagnose disease
Today, during the 85th General Session of the International Association for Dental Research, scientists are reporting that the use of saliva for clinical detection of major human diseases is only a few years away.
Learning the language of DNA
An international consortium of scientists, including a team from The University of Queensland's Institute for Molecular Bioscience (IMB), is a step closer to the next generation of treatments to combat disease, after publishing a comprehensive analysis of the human and mouse transcriptomes.
Study reveals new genes for excessive alcohol drinking
Researchers supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH), have identified new genes that may contribute to excessive alcohol consumption.
'Pregnant' protein-coding genes carry RNA 'babies'
Scientists from the Chinese Academy of Sciences have performed a comprehensive analysis of small, non-protein-coding RNAs in the model nematode, C. elegans.
Solexa and collaborating scientists illuminate the small RNA component of the transcriptome
Solexa, Inc. (Nasdaq: SLXA) today announced that its researchers in collaboration with the Delaware Biotechnology Institute and the University of Delaware reported the most comprehensive analysis to date of the small RNA component of the transcriptome.
Press release from Nature and the Nature Research Journals dated 7 September
NATURE (http://www.nature.com/nature) [1] Uric acid signals danger DOI: 10.1038/nature01991 (http://dx.doi.org/10.1038/nature01991) Uric acid may signal the immune system to warn it of impending danger, according to a paper published online by Nature this week. The research provides a molecular link between cell injury and immunity, and may have implications for vaccines, autoimmunity and inflammation. Cells normally contain uric acid. Now Kenneth L. Rock and colleagues report that when cells are injured, their levels of uric acid go up. When released from dying cells, it stimulates bone-marrow-derived dendritic cells to mature so that they
DNA repair mechanisms are concentrated in the active parts of the genome
Less than 10% of the human genome contains coded information in the form of genes. The 30,000-40,000 genes in the genome are found grouped in discrete regions of the chromosomes. Chemical agents and radiation habitually cause a large variety of injuries to the DNA which interferes in many cell processes, like transcription and replication, and this can cause a loss of control of cell division and the appearance of tumours. In order to avoid this, the human genome contains more than 130 DNA repair genes which are coded by proteins that constantly scrutinise the genome and seek out damage in order to eliminate it. A team of researchers from the Mutation Group at the Department of Genetics and
More Transcriptome News Articles
| © 2008 BrightSurf.com |