Science News - August 28, 2010

particular, two microRNAs, miR- 15 and miR- 16, are missing or found at lower than normal levels in 68 percent of chronic lymphocytic leukemia cases.

Cancer biologists usually lump microRNAs into two groups: those that protect against cancer and those that promote it (though the distinction isn’t perfect). Cancer cells tend to have lower levels of most microRNAs but have an oversupply of a few others.

In the protective corner are microRNAs such as miR- 15 and miR- 16. One of the many proteins regulated by those two microRNAs is BCL2, which keeps cells from pushing the self-destruct button. Cells commit suicide when they become too damaged to operate properly — an important self-defense mechanism for an organism that doesn’t want to walk around with malfunctioning cells. So cells need just the right amount of BCL2 to keep from killing themselves unnecessarily, but not so much of it that they can never die.

The microRNAs pair with messenger RNA to strike the right balance of BCL2. But when miR- 15 and miR- 16 levels are knocked down — which can happen if a copy of a gene is lost or if something goes wrong during microRNA manufacturing — cells make far too much BCL2, essentially disabling the self-destruct mechanism and making cells immortal. Immortality is one hallmark of cancer.

At the opposite end of the spectrum is one of the baddest microRNA bad boys, miR- 21. Elevated levels cause cancer in mice, researchers from Yale University reported online August 8 in Nature. And higher than normal levels have been linked to at least 13 major types of cancer in people and to poor prognoses for people with colon, lung, breast, pancreatic or head and neck cancers, Harris says (SN: 2/2/08, p. 70).

High levels of miR- 21 can slow an important cellular security system involving a protein named p53, researchers from the University of California, Santa Barbara have found. This protein performs multiple protective services, including spurring repair of damaged DNA, halting growth until damage is

DNA codes for the production of a microRNA.

2

A protein called Drosha chops two tails off of the microRNA hairpin.

3

Then the microRNA leaves the nucleus.

A protein called Dicer chops the mature microRNA from the hairpin form.

4

With the help of a protein complex, the mature microRNA hooks up with messenger RNA to block protein production.

1. Genetic variations, breaks in the chromosome, inserted viruses or a lost or duplicated microRNA gene can cause too much or too little of the microRNA to be produced.

2. Drosha may
fail to trim the
microRNA due to
variations in the
microRNA, the pro-
tein or its partners.
work properly, not
enough microRNAs
will be liberated
from the hairpins.
in either the mes-
senger RNA or the
microRNA could
prevent pairing.
Something could
also go wrong with
the proteins that
help the microRNA
;nd the proper
messenger RNA.

Making microRNAs The process by which microRNAs are produced and pair up with messenger RNA (above) is complex, leaving a lot of room for errors like these: