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Cooperation is key—a new way of looking at MicroRNA and how it controls gene expression

ent degradation involves a number of different proteins, including proteins that bind to the AU regions of the mRNA. These binding events may play a role in the stability and degradation of the mRNA. Despite much research over the last few years into exactly how this works, the question had not been answered.

"So far, it has not really been clear what the mechanism is," says Han.

Now, Han and his colleagues are reporting in their Cell paper that the degradation mechanism involves tiny pieces of RNA known as microRNA. These microRNAs, which are generally only 17 or 20 nucleotides, were first identified about 20 years ago, and in the past few years scientists have realized that microRNA is a new category of regulatory molecules and identified hundreds of different microRNA in mammals.

The big question was, what are they doing? About a dozen years ago a few studies came out that showed that microRNA could suppress translation in certain Drosophila (fruit fly) genes if those genes contained sequences complementary to the microRNA's sequence. But finding the targets of these microRNA proved difficult, and by the turn off the century, only a few had been identified.

When the human genome was solved and published in 2001, many scientists thought that the task of finding the mRNA to which the microRNA bound would be relatively straightforward. After all, a short stretch of nucleotides like a microRNA should be expected to bind to a piece of RNA of equal length and complementary sequence. And since these sequences of the microRNA were known, a computer search through the three billion letters of the human genome should find those matching sequences.

But this didn't work. The homology searches yielded far fewer targets than expected and could not account for all known microRNAs. The reason, says Han, is that scientists were trying to predict the microRNA targets using the sequence homology of the full-length microRNAs.

In their
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Source:The Scripps Institute


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