microRNAs regulate thousands of human genes

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Study finds more than one-third of human genome regulated by RNA

15 Jan 2005 Medical News Today

For many years, DNA and proteins have been viewed as the real movers and shakers

in genomic studies, with RNA seen as little more than a messenger that shuttles

information between the two. But researchers from Whitehead Institute for

Biomedical Research and Massachusetts Institute of Technology have discovered

that small RNA molecules called microRNAs regulate thousands of human

genes--more than one third of the genome's protein-coding regions. In other

words, a class of molecule once relegated to the sidelines may be one of the

principal players in regulating cellular mechanisms.

" It's exciting to see how many genes are regulated by microRNAs. We now know

that this type of gene control is much more widespread than previously

appreciated, " says Whitehead Member and MIT professor of biology Bartel.

MicroRNAs interrupt a gene's ability to make protein. These tiny,

single-stranded pieces of RNA are newcomers to biological research. It wasn't

until 2000 that researchers even knew that microRNAs existed in humans. Now, in

the January 14 edition of the journal Cell, , a graduate student

working jointly with Whitehead's Bartel and MIT associate professor of biology

Burge, provides the first evidence that microRNAs influence a large

percentage of life's functions.

The team developed a computational method to define the relationship between

microRNAs and their target genes. In December 2003, the same group identified

400 genes in the human genome targeted by microRNAs. (Prior to this study, there

were no known microRNA targets in any vertebrate.)

In their latest paper, taking advantage of the most recent genome-sequencing

data, the team has compared human genome data with that of the dog, chicken,

mouse, and rat. For each of the microRNAs and protein-coding genes that are

common to these five species, the team looked for correspondence between the

microRNAs and the protein-coding genes. They discovered that regulation of a

third of these genes has been preserved since the last common ancestor of

mammals and chicken, which lived 310 million years ago. " This study is an

excellent example of the power of comparative genomics to illuminate how human

genes are regulated, " says Burge.

" As more genome data becomes available and the technology becomes more

sophisticated, I think we'll find that even more genes are targeted by

microRNAs, " predicts .

In addition, the team discovered some hints about how microRNAs find their

targets.

To produce a protein, the cell first makes a template for that protein by

constructing a molecule called messenger RNA. MicroRNAs inhibit protein

production by associating themselves with particular messenger RNAs, thereby

reducing the amount of protein that's ultimately produced. In this study, the

researchers determined which portion of the microRNA is most important for this

process, and identified additional determinants in the messenger RNA that are

likely to contribute to recognition by microRNAs.

These findings contribute to the recent interest in potential therapeutic uses

of RNA. For example, using a technique known as RNA interference, or RNAi,

researchers are shutting off genes by delivering into cells artificial

microRNA-like molecules called siRNAs. RNAi has already transformed how many

labs are investigating gene functions, and siRNAs are being developed for

clinical applications. Learning more about how microRNAs operate in human cells

should help scientists to understand how best to exploit siRNAs for treating

disease.

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