In Stevens and colleagues found penta snRNP

In 2002, Stevens and colleagues found penta-snRNP, which contains all five spliceosomal snRNAs and over 60 pre-mRNA splicing factors, in yeast. They proposed that penta-snRNP associates prior to pre-mRNA substrate binding rather than with the pre-mRNA based on the results of a stepwise addition of discrete snRNPs (Stevens et al., 2002). Penta-snRNP is an effective complex in vivo because the maximum rate of RNA processing is approximately 40–80bp/s (Dennis and Bremer, 1974). Because the hPS genome is transcriptionally hyperactive and most pre-mRNA splicing occurs co-transcriptionally, it would be interesting to exploit whether hPS spliceosomes are related to the penta-snRNP complex. While recent studies have demonstrated the pivotal role of the splicing factors MBNL1/2, RBM24, RBFOX2, SRSF3, and ESRP1 in cell fate changes and pluripotency (Cieply et al., 2016; Fagoonee et al., 2013; Gabut et al., 2011; Han et al., 2013; Venables et al., 2013; Zhang et al., 2016), the underlying mechanisms remain largely unknown. We believe that a precise understanding of pluripotency-specific spliceosome function might further our understanding of the complicated splicing mechanisms underlying pluripotency control.
Conclusion The following are the supplementary data related to this article.
Acknowledgments We are grateful to Dr. Florian Heyd at Free University in Berlin for providing the mini-gene and for discussions and suggestions. We are grateful to Sun-Young Kim at Korea Research Institute of Bioscience and Biotechnology for discussion and advice. This work was supported by NRF grants (2012M3A9C7050224 and 2017R1A2B2012190) and by an NST Grant (CRC-15-02-KRIBB).
Introduction Oligodendrocytes, the cells wrapping the Calcitriol of the central nervous system (CNS) with the myelin sheath, derive from the oligodendrocyte precursor cells (OPCs) generated during development from multipotent neuroectodermal derivatives in the cortex and spinal cord (Bergles and Richardson, 2015). These cells proliferate and migrate to populate the entire adult CNS, where they account for approximately 5–8% of the entire cell population (Dawson et al., 2003). New OPCs can be also generated in the adult CNS from neural stem cells (NSCs; Agathou et al., 2013) and by mitosis, as OPCs are the major proliferating population of the CNS under appropriate stimuli (Fernandez-Castaneda and Gaultier, 2016). These cells are responsible for myelin formation during development (Bergles and Richardson, 2015), and for myelin turnover and repair during adulthood (Young et al., 2013). The process of myelin formation is highly orchestrated in time and space, involves different cell types, and a key step of this process is the OPC maturation toward myelinating oligodendrocyte (Zuchero and Barres, 2013). Internal and external cues targeting genetic, epigenetic and cytoplasmic mechanisms provide the appropriate microenvironment that regulates the molecular machinery triggering OPCs out of the cell cycle to terminal differentiation (Zuchero and Barres, 2013; Liu et al., 2016; Fernández et al., 2016). It has been suggested that remyelination after lesions in the adult CNS recapitulates developmental myelination (Franklin and Hinks, 1999). However, substantial differences could well be expected between a normal turnover process and a repair process (Fancy et al., 2011) triggered by pathological events like inflammation and hypoxic/ischemic damage. These events actually mobilize a large number of inhibitory factors leading to a differentiation block of OPC (Gaesser and Fyffe-Maricich, 2016). Thus, there is an urgent need to more clearly elucidate the molecular bases of the relationship between OPCs proliferation and differentiation, carefully dissecting developmental myelination vs. myelin turnover in adulthood, and physiological vs. pathological conditions. In the present study, we investigated the role of poly(ADP-ribose) polymerases (PARPs) in OPCs survival, proliferation and differentiation. PARPs are members of nuclear enzyme family that catalyse the formation of (ADP-ribose)n chains from NAD+ on acceptor proteins after DNA double strands breaks (Amé et al., 2004). Because of the PARPs well described role in DNA repair and apoptosis induction (Heeres and Hergenrother, 2007), PARPs inhibition is currently considered a therapeutic option for cancer, including glioblastoma (Curtin and Szabo, 2013). Moreover, PARPs inhibition was proposed as a neuroprotective strategy for neonatal asphyxia and hypoxia/ischemia encephalopathy (Neira-Peña et al., 2015), a CNS injury that occurs during a critical period of developmental myelination (Dimou and Götz, 2014). In order to study the effect of PARP inhibition in all stages of differentiation, from NSCs to mature oligodendrocytes, we used OPCs-enriched cultures obtained from the fetal forebrain- and the adult sub-ventricular zone of the mouse to study the different role of PARPs in adult and fetal OPCs differentiation and maturation. We used PARP inhibitors having a different inhibitory concentration as pharmacological toll, including the clinically approved Olaparib (LYNPARZA™).