Česká Genetická Banka

SCIENCE 11. 1. 2013

SCIENCE: NEUROSCIENCE: Developmental Refining of Neuroglial Signaling?

"When the term neuroglia (“nerve-putty”) was introduced by the German pathologist Rudolf Virchow in 1856 (1), it was like a stigma, distracting any reputable neuroscientist from doing research on these cells. More than a century later, intense research on glial cells was performed and culminated in the concept of the tripartite synapse, according to which astrocytes (a main type of glia) respond to neuronal activity by increasing their internal calcium (Ca^2÷) concentration, which triggers the release of chemical transmitters from glia themselves and, in turn, causes feedback regulation of neuronal activity and synaptic strength (2). Although this concept became widely accepted among neuroscientists, it has now been challenged. On page 197 in this issue, Sun et al. (3) find that neuronglia signaling in the adult brain may occur in a manner fundamentally distinct from that exhibited during development."

http://www.sciencemag.org/content/339/6116/152.summary

 

NATURE: Control of somatic tissue differentiation by the long non-coding RNA TINCR

"Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized^{1, 2, 3, 4}; however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7-kilobase lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism. TINCR is required for high messenger RNA abundance of key differentiation genes, many of which are mutated in human skin diseases, including FLG, LOR, ALOXE3, ALOX12B, ABCA12, CASP14 and ELOVL3. TINCR-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale RNA interactome analysis revealed that TINCR interacts with a range of differentiation mRNAs. TINCR–mRNA interaction occurs through a 25-nucleotide ‘TINCR box’ motif that is strongly enriched in interacting mRNAs and required for TINCR binding. A high-throughput screen to analyse TINCR binding capacity to approximately 9,400 human recombinant proteins revealed direct binding of TINCR RNA to the staufen1 (STAU1) protein. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Loss of UPF1 and UPF2, both of which are required for STAU1-mediated RNA decay, however, did not have differentiation effects. Instead, the TINCR–STAU1 complex seems to mediate stabilization of differentiation mRNAs, such as KRT80. These data identify TINCR as a key lncRNA required for somatic tissue differentiation, which occurs through lncRNA binding to differentiation mRNAs to ensure their expression."

http://www.nature.com/nature/journal/v493/n7431/full/nature11661.html

 

NATURE: Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis

"Mechanisms controlling the proliferative activity of neural stem and progenitor cells (NSPCs) have a pivotal role to ensure life-long neurogenesis in the mammalian brain¹. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis², is highly active in adult NSPCs and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene previously implicated in lipid metabolism^{3, 4, 5}, that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA⁶, which is an essential substrate for Fasn to fuel lipogenesis. Thus, we identify here a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation."

http://www.nature.com/nature/journal/v493/n7431/full/nature11689.html