The synthesis of ribosomal proteins (RPs) has long been known to be a process strongly linked to the growth status of the cell. In vertebrates, this coordination is dependent on RP mRNA translational efficiency, which changes according to physiological circumstances. Despite many years of investigation, the trans‐acting factors and the signaling pathways involved in this regulation are still elusive. At the same time, however, new techniques and classic approaches have opened up new perspectives as regards RP regulation and function. In fact, the proteasome seems to play a crucial and unpredicted role in regulating the availability of RPs for subunit assembly. In addition, the study of human ribosomal pathologies and animal models for these diseases has revealed that perturbation in the synthesis and/or function of an RP activates a p53‐dependent stress response. Surprisingly, the effect of the ribosomal stress is more dramatic in specific physiological processes: hemopoiesis in humans, and pigmentation in mice. Moreover, alteration of each RP impacts differently on the development of an organism.
miR-34a is involved in the regulation of the fate of different cell types. However, the mechanism by which it controls the differentiation programme of neural cells remains largely unknown. Here, we investigated the role of miR-34a in neurogenesis and maturation of developing neurons and identified Doublecortin as a new miR-34a target. We found that the overexpression of miR-34a in vitro significantly increases precursor proliferation and influences morphology and function of developing neurons. Indeed, miR-34a overexpressing neurons showed a decreased expression of several synaptic proteins and receptor subunits, a decrement of NMDA-evoked current density and, interestingly, a more efficient response to synaptic stimulus. In vivo, miR-34a overexpression showed stage-specific effects. In neural progenitors, miR-34a overexpression promoted cell proliferation, in migratory neuroblasts reduced the migration and in differentiating newborn neurons modulated process outgrowth and complexity. Importantly, we found that rats overexpressing miR-34a in the brain have better learning abilities and reduced emotionality.
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