Researchers identify noncoding RNA crucial for stem cell suppression in the brain.

While thousands of long noncoding RNAs (lncRNAs) have been identified, few lncRNAs that control neural stem cell (NSC) behavior are known. Here, we identify Pinky (Pnky) as a neural-specific lncRNA that regulates neurogenesis from NSCs in the embryonic and postnatal brain. In postnatal NSCs, Pnky knockdown potentiates neuronal lineage commitment and expands the transit-amplifying cell population, increasing neuron production several-fold. Pnky is evolutionarily conserved and expressed in NSCs of the developing human brain. In the embryonic mouse cortex, Pnky knockdown increases neuronal differentiation and depletes the NSC population. Pnky interacts with the splicing regulator PTBP1, and PTBP1 knockdown also enhances neurogenesis. In NSCs, Pnky and PTBP1 regulate the expression and alternative splicing of a core set of transcripts that relates to the cellular phenotype. These data thus unveil Pnky as a conserved lncRNA that interacts with a key RNA processing factor and regulates neurogenesis from embryonic and postnatal NSC populations. The Long Noncoding RNA Pnky Regulates Neuronal Differentiation of Embryonic and Postnatal Neural Stem Cells. Lim et al 2015.

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 opensource study, published in the journal 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.

The team state that 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,’ and has only been found in the brain so far.

The researchers 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.  These findings suggest that Pnky, and perhaps lncRNAs in general, could eventually have important applications in regenerative medicine and cancer treatment.

Using an analytical technique called mass spectrometry the team found that Pnky binds the protein PTBP1, which is also found in brain tumours and is known to be a driver of brain tumour growth. In neural stem cells, Pnky and PTBP1 appear to function together to suppress the production of neurons. The current study found that if one or the other is taken away the stem cells differentiate, making more neurons.  It is also possible that Pnky can regulate brain tumour growth, which means, the team say, that they may have identified a target for the treatment of brain tumours.

The researchers state 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; adding recently, over fifty thousand human lncRNAs have been discovered.

The team surmise that the current data suggest there may be more human lncRNAs than there are genes that code for proteins  It is possible that not all lncRNAs have important biological functions, however, the medical community 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 lab state that they are right there on the frontier.

Source:  UC San Francisco 

While thousands of long noncoding RNAs (lncRNAs) have been identified, few lncRNAs that control neural stem cell (NSC) behavior are known. Here, we identify Pinky (Pnky) as a neural-specific lncRNA that regulates neurogenesis from NSCs in the embryonic and postnatal brain. In postnatal NSCs, Pnky knockdown potentiates neuronal lineage commitment and expands the transit-amplifying cell population, increasing neuron production several-fold. Pnky is evolutionarily conserved and expressed in NSCs of the developing human brain. In the embryonic mouse cortex, Pnky knockdown increases neuronal differentiation and depletes the NSC population. Pnky interacts with the splicing regulator PTBP1, and PTBP1 knockdown also enhances neurogenesis. In NSCs, Pnky and PTBP1 regulate the expression and alternative splicing of a core set of transcripts that relates to the cellular phenotype. These data thus unveil Pnky as a conserved lncRNA that interacts with a key RNA processing factor and regulates neurogenesis from embryonic and postnatal NSC populations.  The Long Noncoding RNA Pnky Regulates Neuronal Differentiation of Embryonic and Postnatal Neural Stem Cells.  Lim et al 2015.
While thousands of long noncoding RNAs (lncRNAs) have been identified, few lncRNAs that control neural stem cell (NSC) behavior are known. Here, we identify Pinky (Pnky) as a neural-specific lncRNA that regulates neurogenesis from NSCs in the embryonic and postnatal brain. In postnatal NSCs, Pnky knockdown potentiates neuronal lineage commitment and expands the transit-amplifying cell population, increasing neuron production several-fold. Pnky is evolutionarily conserved and expressed in NSCs of the developing human brain. In the embryonic mouse cortex, Pnky knockdown increases neuronal differentiation and depletes the NSC population. Pnky interacts with the splicing regulator PTBP1, and PTBP1 knockdown also enhances neurogenesis. In NSCs, Pnky and PTBP1 regulate the expression and alternative splicing of a core set of transcripts that relates to the cellular phenotype. These data thus unveil Pnky as a conserved lncRNA that interacts with a key RNA processing factor and regulates neurogenesis from embryonic and postnatal NSC populations. The Long Noncoding RNA Pnky Regulates Neuronal Differentiation of Embryonic and Postnatal Neural Stem Cells. Lim et al 2015.
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