RNA molecules have long been known for their role in translating
genes to proteins inside a cell, but more recently, scientists have
found large numbers of RNA molecules that don't code for proteins but
seem to have other cellular roles. Most research in mammals has focused
on tiny RNA molecules called microRNAs, but a new study, published this
week in Nature,
describes the far-reaching effects of much larger and relatively
unstudied RNA molecules called lincRNAs (short for large intergenic
noncoding RNAs). The study identifies lincRNAs that play a role in the
function of embryonic stem cells, and suggests trying to use lincRNAs to
manipulate these cells to spawn other cell types.
Missing link: Large RNA molecules called lincRNAs turn out to
have an important role in controlling the function and fate of embryonic
stem cells, like those pictured here.
Mitchell Guttman, first author of the study and a graduate student
at MIT and the Broad Institute, says that when the Broad team discovered
more than 3,500 unique lincRNAs in the human and mouse genomes in 2009,
"the potential was enormous, and we wanted to know what they could be
doing."
To answer that question, the researchers focused on understanding
lincRNAs' role in embryonic stem cells. Using a technique called RNA
interference, they systematically shut down the function of each of more
than 200 lincRNAs previously identified as playing a role in embryonic
stem cells. They then profiled the genes expressed in the cells and
studied their functions. They found that most lincRNAs have widespread
effects on cells, and that they help control the fate of stem cells. The
team identified about two dozen lincRNAs that help maintain the cell's
pluripotency—its ability to beget all other kinds of cells—and a similar
number of lincRNAs that repress genes involved in differentiating into
other cell types.
Nudging stem cells to differentiate has proved challenging so far,
and scientists have been looking for better ways. Guttman says that
inhibiting lincRNAs in specific combinations may make it possible to
direct stem cells to transform in specific ways. George Daley,
a stem-cell biologist at Harvard Medical School and Children's Hospital
Boston, says that further probing the effects of lincRNAs "will help
refine our capacity to control and manipulate cells in culture, and this
will advance the utility of stem cells for regenerative medicine."
Tariq Rana,
an RNA biologist at Sanford-Burnham Medical Research Institute in La
Jolla, California, calls the work "the first comprehensive study
defining the functional roles of lincRNAs in embryonic stem cells." He
says it will launch new investigations into how lincRNAs regulate gene
expression.
Guttman and colleagues propose that lincRNAs have an important
coordinating function in the cell: like sergeants commanding military
units, single lincRNAs seem to interact with and control large complexes
of proteins. He says that these large RNAs also seem to be put together
in a modular way, like molecular Tinkertoys. Learning how they're put
together could allow scientists to design and assemble RNAs to perform
very specific tasks—and manipulate cells.
By Courtney Humphries
From Technology Review
0 comments:
Post a Comment