113 research outputs found

    Translation on demand by a simple RNA-based thermosensor

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    Structured RNA regions are important gene control elements in prokaryotes and eukaryotes. Here, we show that the mRNA of a cyanobacterial heat shock gene contains a built-in thermosensor critical for photosynthetic activity under stress conditions. The exceptionally short 5′-untranslated region is comprised of a single hairpin with an internal asymmetric loop. It inhibits translation of the Synechocystis hsp17 transcript at normal growth conditions, permits translation initiation under stress conditions and shuts down Hsp17 production in the recovery phase. Point mutations that stabilized or destabilized the RNA structure deregulated reporter gene expression in vivo and ribosome binding in vitro. Introduction of such point mutations into the Synechocystis genome produced severe phenotypic defects. Reversible formation of the open and closed structure was beneficial for viability, integrity of the photosystem and oxygen evolution. Continuous production of Hsp17 was detrimental when the stress declined indicating that shutting-off heat shock protein production is an important, previously unrecognized function of RNA thermometers. We discovered a simple biosensor that strictly adjusts the cellular level of a molecular chaperone to the physiological need

    Restriction of trophic factors and nutrients induces PARKIN expression

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    Parkinson’s disease (PD) is the most frequent neurodegenerative movement disorder and manifests at old age. While many details of its pathogenesis remain to be elucidated, in particular the protein and mitochondrial quality control during stress responses have been implicated in monogenic PD variants. Especially the mitochondrial kinase PINK1 and the ubiquitin ligase PARKIN are known to cooperate in autophagy after mitochondrial damage. As autophagy is also induced by loss of trophic signaling and PINK1 gene expression is modulated after deprivation of cytokines, we analyzed to what extent trophic signals and starvation stress regulate PINK1 and PARKIN expression. Time course experiments with serum deprivation and nutrient starvation of human SH-SY5Y neuroblastoma cells and primary mouse neurons demonstrated phasic induction of PINK1 transcript up to twofold and PARKIN transcript levels up to sixfold. The corresponding threefold starvation induction of PARKIN protein was limited by its translocation to lysosomes. Analysis of primary mouse cells from PINK1-knockout mice indicated that PARKIN induction and lysosomal translocation occurred independent of PINK1. Suppression of the PI3K-Akt-mTOR signaling by pharmacological agents modulated PARKIN expression accordingly. In conclusion, this expression survey demonstrates that PARKIN and PINK1 are coregulated during starvation and suggest a role of both PD genes in response to trophic signals and starvation stress

    In search of morphological modules: a systematic review

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    Morphological modularity arises in complex living beings due to a semi-independent inheritance, development, and function of body parts. Modularity helps us to understand the evolvability and plasticity of organismal form, and how morphological variation is structured during evolution and development. For this reason, delimiting morphological modules and establishing the factors involved in their origins is a lively field of inquiry in biology today. Although it is thought that modularity is pervasive in all living beings, actually we do not know how often modularity is present in different morphological systems. We also do not know whether some methodological approaches tend to reveal modular patterns more easily than others, or whether some factors are more related to the formation of modules or the integration of the whole phenotype. This systematic review seeks to answer these type of questions through an examination of research investigating morphological modularity from 1958 to present. More than 200 original research articles were gathered in order to reach a quantitative appraisal on what is studied, how it is studied, and how the results are explained. The results reveal an heterogeneous picture, where some taxa, systems, and approaches are over-studied, while others receive minor attention. Thus, this review points out various trends and gaps in the study of morphological modularity, offering a broad picture of current knowledge and where we can direct future research efforts
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