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RNA study finds activity in ‘silent’ regions of human genome


A much larger proportion of the human genome is involved in producing the body's diverse collection of RNAs than was previously believed. The amount of DNA needed to generate and maintain these RNAs may be ten times greater than that which encodes all human proteins, according to a new study.

Detail from comparative maps generated during RNA analysis of chromosomes 21 and 22. View full

Thomas R. Gingeras, of Affymetrix Inc., in Santa Clara, California, and colleagues detected new areas of transcriptional activity along human chromosomes 21 and 22 using gene chips. The chips contain ‘probes’ that bind RNA and produce a fluorescent signal. Many signals came from gene-poor regions of the chromosomes, which had previously been considered ‘silent’; more than half the RNAs occurred hundreds to tens of thousands of base pairs away from the nearest gene.

"These results suggest that there is considerable more transcription than can be accounted for by counting the DNA sequences in the regions known to contain genes," says Gingeras. The RNA for the well-characterized 770 genes on the chromosomes 21 and 22 added up to a tenth of the total RNA detected by the researchers.

It is not yet known what all these RNAs, or transcripts, do in the cell, but the researchers are confident that they have biological functions. The transcripts came from a pool of RNA in the cytoplasm, which means they survived in the cell for a period of time and were transported from the nucleus.

"The cell thinks these transcripts are important enough to preserve them and expends the energy to transport them to the cytoplasm," says Gingeras. The RNAs, he adds, may have roles in regulating the production and structure of proteins.

A second line of evidence that the RNAs have an important biological function is that similar transcripts have been identified in other species, according to Gingeras. The sequence conservation of many of these novel transcribed regions during evolution suggests that the RNAs have a role of some sort.

The researchers analyzed the raw signals from the gene chips, eliminated noise and false signals, and created chromosomal maps of transcriptional activity. The maps, which appear in Science, are part of a project by the Affymetrix team and the US National Cancer Institute (NCI) to profile RNA activity across the entire human genome.

The NCI wants to know, for instance, how the production of RNA changes during certain cancers. The study used cells from ten different cancer types and one colony of fetal cells. The raw data from the chips and the maps are available to researchers on the Web sites of the NCI and the University of California, Santa Cruz.

"What drove this study was the fact that we had a draft human genome sequence and technology that allows us to determine where we could detect RNA along the whole genome," says Gingeras. "So we did the experiment."

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Kapranov, P. et al. Large-scale transcriptional activity in chromosomes 21 and 22. Science 296, 916-919 (May 3, 2002).

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