Exosc2 assembles into a complex with components homologous to bacterial 3’ to 5’ exoribonuclease (PNPase) ( Mitchell et al., 1997). Mutations of Exosc2 (Rrp4) disrupt 5.8S rRNA 3’-end processing ( Mitchell et al., 1996). The first subunit was discovered from an analysis of mechanisms controlling yeast rRNA synthesis. The highly conserved exosome complex, an RNA-degrading and processing machine, is expressed in all eukaryotic cells ( Januszyk and Lima, 2014 Kilchert et al., 2016). Furthermore, it is worth exploring whether this new knowledge can help efforts to produce red blood cells on an industrial scale, which could then be used to treat patients with conditions such as anemia. In future, it will be important to study the exosome complex in living mice and in human cells, and to see whether it also controls other signaling pathways. Thus, normal levels of the exosome complex keep the delicate balance between proliferation and differentiation, which is crucial to the development of red blood cells. Lastly, although the experimental cells could no longer respond to these proliferation signals, they could react to erythropoietin, which promotes differentiation. Normally, SCF interacts with Kit to instruct cells to multiply. Further experiments showed that cells with less of the exosome complex also made less of a protein named Kit. The experiments showed that these cells were no longer able to respond when treated with SCF in culture, whereas the control cells responded as normal. set out to address this issue by isolating precursor cells with the potential to become red blood cells from mouse fetal livers and experimentally reducing the levels of the exosome complex. However, it was not clear how the exosome complex sets up the differentiation block and whether it is somehow connected to the signaling from SCF and erythropoietin. The exosome complex controls several processes within cells by modifying or degrading a variety of messenger RNAs, the molecules that serve as intermediates between DNA and protein. Previous work has shown that a collection of proteins called the exosome complex can block steps leading towards mature red blood cells. It is important to maintain this balance between these two processes because too much proliferation can lead to cancer while too much differentiation will exhaust the supply of stem cells. To replenish the red blood cells that are lost, first a protein called stem cell factor (SCF) instructs stem cells and precursor cells to proliferate, and a second protein, known as erythropoietin, then signals to these cells to differentiate into mature red blood cells. These cells circulate for a certain amount of time before they die. Red blood cells supply an animal’s tissues with the oxygen they need to survive. Functioning as a gatekeeper of this developmental signaling transition, the exosome complex controls the massive production of erythroid cells that ensures organismal survival in homeostatic and stress contexts. Exosome complex integrity in erythroid precursor cells ensures Kit receptor tyrosine kinase expression and stem cell factor/Kit signaling, while preventing responsiveness to erythropoietin-instigated signals that promote differentiation. While dissecting requirements for the maturation barricade in Mus musculus, we discovered that the exosome complex is a vital determinant of a developmental signaling transition that dictates proliferation/amplification versus differentiation. Previously, we demonstrated that exosome complex subunits confer an erythroid maturation barricade, and the erythroid transcription factor GATA-1 dismantles the barricade by transcriptionally repressing the cognate genes. How this post-transcriptional RNA-regulatory machine impacts cell fate decisions and differentiation is poorly understood. Since the highly conserved exosome complex mediates the degradation and processing of multiple classes of RNAs, it almost certainly controls diverse biological processes.
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