November 2017

Bio-Synthesis Newsletter - November 2017

RNA helices transport mRNA

2KUU-K10-TLSRNAIn drosophila, A’-form RNA helices drive microtubule-based mRNA transport. Bullock et al., in 2010, used NMR spectroscopy to describe the first tertiary structure of an RNA element responsible for mRNA transport. Microtubule-based mRNA transport is used to restrict protein expression in the cell. Specific protein expression defines cell polarity and axis determination for neuronal function. The report of this structure adds to our understanding of cis-acting mRNA localization signals by molecular motor complexes. The K10 transport localization element is a 44 nucleotide regulatory element. This RNA structure is responsible for the transport and anterior localization of k10 mRNA in the oocyte in which it establishes dorsoventral polarity. 

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PEDF determines Stem Cell Fate

PEDF-1IMV Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein widely expressed in multiple organs. PEDF exhibits multiple functions including antiangiogenic, antitumor, anti-inflammatory, and neurotrophic properties, among others. PEDF is important for bone development as well as for the modulation of resident stem cell populations in the brain, muscle, and eye. PEDF also promotes stem cell renewal, and two functional epitopes have been identified. A PEDF-derived short peptide (PSP) is known to induce satellite cell proliferation and promotes muscle regeneration. Whereas a 44-amino acid peptide fragment of PEDF binds receptors on the surfaces of different neuron types were it determines neurotrophic activity and neuronal differentiation.

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Engineering RNA as a molecular motor

Scallop-myosin-1KK7 Researchers have recently shown that strands of RNA can be used as part of a molecular motor. A research group has now created a molecular motor in which RNA replaces the protein arm of myosin. This new protein-RNA hybrid is reported to move faster than previously designed protein motors or DNA motors. Also, the direction of motion can be changed by adding DNA strands with specific sequences. A tetramer form of this motor system was demonstrated to walk along a fixed actin filament at speeds of 10 to 20 nm per second. The goal is using this type of motors as a molecular delivery system in living cells.  

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Edaravone, a new drug for ALS

Edaravone-or-Radicava The drug edaravone or radicaval is now approved for the treatment of amyotrophic lateral sclerosis (ALS). ALS is a progressive, adult-onset fatal disease. Edaravone is a neuroprotective drug with properties of a free radical scavenger. In the central nervous system, edaravone acts as a potent scavenger of oxygen radicals. Presently, it is thought that edaravone potentially reduces oxidative stress. In ALS mouse models, it was shown that edaravone suppresses motor function decline and nitration of tyrosine residues in the cerebrospinal fluid. Protein tyrosine nitration under disease conditions is a commonly observed chemical modification. Tyrosine nitration, for example in peptides or proteins, is mediated by reactive nitrogen species such as the peroxynitrite anion as well as nitrogen dioxide radicals.   

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