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
of a microRNA.
A protein called
Drosha chops two
tails off of the
A protein called Dicer
chops the mature
microRNA from the
With the help of a protein
complex, the mature
microRNA hooks up with
messenger RNA to block
1. Genetic variations, breaks in
inserted viruses or
a lost or duplicated
can cause too
much or too little
of the microRNA to
2. Drosha may
fail to trim the
microRNA due to
variations in the
microRNA, the pro-
tein or its partners.
work properly, not
will be liberated
from the hairpins.
in either the mes-
senger RNA or the
also go wrong with
the proteins that
help the microRNA
;nd the proper
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:
3. If Dicer levels
are too low or if
the protein doesn’t
4. Messenger RNA
decoys could dis-
tract the microRNAs
from their intended
target, or mutations
August 28, 2010 | SCIENCE NEWS | 19