A research team at UC
San Francisco has discovered an RNA molecule called Pnky that can be
manipulated to increase the production of neurons from neural stem cells.
The research, led by
neurosurgeon Daniel A. Lim, MD, PhD, and published on March 19, 2015 in Cell
Stem Cell, has possible applications in regenerative medicine, including
treatments of such disorders as Alzheimer’s disease, Parkinson’s disease and
traumatic brain injury, and in cancer treatment.
Co-first authors Alex
Ramos, PhD, and Rebecca Andersen, who are students in Lim’s laboratory, first
studied Pnky in neural stem cells found in mouse brains, and also identified
the molecule in neural stem cells of the developing human brain. They found that
when Pnky was removed from stem cells in a process called knockdown, neuron
production increased three to four times.
“It is remarkable that
when you take Pnky away, the stem cells produce many more neurons,” said Lim,
an assistant professor of neurological surgery and director of restorative
surgery at UCSF.
“These findings suggest that Pnky, and perhaps lncRNAs in general,
could eventually have important applications in regenerative medicine and
cancer treatment.”
Lim observed that Pnky
has an intriguing possible connection with brain tumors.
Pnky is one of a
number of newly discovered long noncoding RNAs (lncRNAs), which are stretches
of 200 or more nucleotides in the human genome that do not code for proteins,
yet seem to have a biological function.
The name, pronounced
“Pinky,” was inspired by the popular American cartoon series Pinky and the
Brain. “Pnky is encoded near a gene called ‘Brain,’ so it sort of suggested
itself to the students in my laboratory,” said Lim. Pnky also appears only to
be found in the brain, he noted.
Using an analytical
technique called mass spectrometry, Ramos found that Pnky binds the protein
PTBP1, which is also found in brain tumors and is known to be a driver of brain
tumor growth. In neural stem cells, Pnky and PTBP1 appear to function together
to suppress the production of neurons. “Take away one or the other and the stem
cells differentiate, making more neurons,” said Lim. “It is also possible that
Pnky can regulate brain tumor growth, which means we may have identified a
target for the treatment of brain tumors.”
Lim said that the
larger significance of the research is that it adds to a growing store of
knowledge about lncRNAs, previously unknown sections of the genome that some
biologists have referred to as the “dark matter” of the human genome.
“Recently, over fifty
thousand human lncRNAs have been discovered. Thus, there may be more human
lncRNAs than there are genes that code for proteins,” said Lim. “It is possible
that not all lncRNAs have important biological functions, but we are making a
start toward learning which ones do, and if so, how they function. It’s a new
world of experimental biology, and the students in my lab are right there on
the frontier.”
Lim had particular
praise for Ramos, an MD-PhD student in the UCSF Medical Scientist Training
Program, and Andersen, who has a fellowship from the prestigious National
Science Foundation (NSF) Graduate Research Fellowship Program. “They have been
a great collaborative team and an inspiration to others in my lab,” said Lim.
“I think they represent the pioneering, investigative spirit of the UCSF
student body.”
Comentários
Enviar um comentário