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Novel method identifies 'hidden' genes

ers in Bartel's lab to take a closer look at this phenomenon. They found a new world of tiny regulatory RNAs present in a broad range of organisms, including worms, humans, fish and plants.

"The regulatory role for RNA had historically been under-appreciated, as researchers focused primarily on proteins as gene regulators. We are excited about the extent to which these small miRNAs also appear to be involved in normal gene regulation," said Bartel.

In March 2003, Bartel and Burge auditioned their new computational approach, called MiRscan. That work, published in the March 7 issue of Science, streamlined the search for miRNAs by giving researchers an estimate of how many miRNAs are nestled within the vertebrate genomes, such as those of humans and mice.

To generate this estimate, the researchers compared candidate miRNA sequences found in mice and humans to those found the puffer fish Fugu rubripes, a distant relative of mice and humans. Puffer fish share many of the same genes and regulatory sequences as humans, but have a much smaller genome, making it easier to identify key genes and regulatory sequences. The researchers found 15,000 genomic segments that were known to exist outside of the protein-coding regions in the human, mouse and puffer fish genomes but still appear to have been retained since the last common ancestor of fish and mammals.

Lee Lim, then a postdoctoral researcher in both the Bartel and Burge labs and the tool's chief architect, used MiRscan to cross-examine these 15,000 genomic segments and accurately predict which were likely to be microRNA genes. The researchers found most of the human microRNAs and estimated that there are at least 200 but no more than 250 human genes coding for microRNAs.

The paper published this week describes MiRscan and how it was developed to identify miRNAs in C. elegans. Bartel and his colleagues have now found and confirmed nearly 90 miRNA genes in C. elegans and estimate
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Contact: Kelli Whitlock or Melissa Withers
newsroom@wi.mit.edu
617-258-5183
Whitehead Institute for Biomedical Research
17-Apr-2003


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