1,721,155 research outputs found
Cooperativity in RNA-protein interactions: The complex is more than the sum of its partners
No full textMutations in RNA-binding proteins (RBPs) are often linked to specific neurological disorders, suggesting that each of these RBPs regulates a particular neuronal function. Instead, they recognise many mRNAs and often participate in various post-transcriptional processes. To gain specificity, RBPs bind to RNA in collaboration with other RBPs. This model also explains how an RBP can play diverse roles: many RBPs do not contain an effector domain, which joins the RNA-protein complex as an additional unit. Different complexes, even if anchored on the same RBP, recruit diverse effectors. Therefore, the combination of RBPs determines the fate of an mRNA. We argue that new experimental and bioinformatic paradigms are needed to elucidate the combination of RBPs acting on a given mRNA
A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders
No full textAltered synaptic structure and function is a major hallmark of fragile X syndrome (FXS), autism spectrum disorders (ASDs), and other intellectual disabilities (IDs), which are therefore classified as synaptopathies. FXS and ASDs, while clinically and genetically distinct, share significant comorbidity, suggesting that there may be a common molecular and/or cellular basis, presumably at the synapse. In this article, we review brain architecture and synaptic pathways that are dysregulated in FXS and ASDs, including spine architecture, signaling in synaptic plasticity, local protein synthesis, (m) RNA modifications, and degradation. mRNA repression is a powerful mechanism for the regulation of synaptic structure and efficacy. We infer that there is no single pathway that explains most of the etiology and discuss new findings and the implications for future work directed at improving our understanding of the pathogenesis of FXS and related ASDs and the design of therapeutic strategies to ameliorate these disorders
SnapShot: FMRP interacting proteins
No full textThe Fragile X syndrome, caused by the absence or mutation of fragile X mental retardation protein, FMRP, is a the common component of inherited intellectual disability and autism. This SnapShot surveys the protein interaction partners of FMRP, focusing on the cellular pathways in which they are involved
Gender Equality from a European Perspective: Myth and Reality
Full text linkIn the past 50 years, significant progress in women’s equality has been made worldwide. Western countries, particularly European countries, have implemented initiatives to attain a more gender-balanced workforce with the introduction of family friendly policies, by trying to narrow the gender pay gap and by promoting women’s career progression. In academia, however, fewer women reach top leadership positions than those in the political arena. These findings suggest that academia needs to carefully evaluate why these new policies have not been very effective. In this NeuroView, we report on the progress made in higher education, the shortcomings, and how new initiatives hold great promise for improving gender equality in academia around the globe
SnapShot: FMRP mRNA targets and diseases
No full textFMRP, or fragile X mental retardation protein is an RNA-binding protein. Mutations in the FMRP protein have been associated with neurological disease as have a number of its mRNA-binding targets. This SnapShot presents 40 bona fide FMRP targets for which mRNA binding and protein regulation have been robustly reported in mammals along with the diseases with which they have been associated
Gar1p binds to the small nucleolar RNAs snR10 and snR30 in vitro through a nontypical RNA binding element
Full text linkThe nucleolar proteins Gar1p and fibrillarin possess a typical nucleolar glycine/arginine-rich domain and belong to ribonucleoprotein particles. Both proteins are essential for yeast cell growth and are required for pre-rRNA processing. In addition, Gar1p is involved in pre-rRNA pseudouridylation, whereas fibrillarin is required for pre-rRNA methylation. Gar1p and fibrillarin are each associated with a different subset of the small nucleolar RNAs (snoRNAs). Gar1p is co-immunoprecipitated with the H/ACA family of snoRNAs, whereas fibrillarin is co-immunoprecipitated with the C/D family. However, attempts to demonstrate direct interactions between fibrillarin and snoRNAs have failed, and such interactions between Gar1p and the H/ACA snoRNAs had not yet been reported. Among the H/ACA snoRNAs associated with Gar1p, one can distinguish a large group of snoRNAs that are not essential in yeast and serve as guides for pseudouridine synthesis onto the pre-rRNA molecule. In contrast, the two snoRNAs snR10 and snR30 are required for normal cell growth and for pre-rRNA cleavage. We show here that Gar1p interacts in vitro directly and specifically with these two snoRNAs. Deletion analysis of Gar1p indicates that a major RNA binding element, which is extremely well conserved throughout evolution, lies in the middle of the protein. However, this domain alone binds poorly to the target RNAs and an accessory domain is required to restore efficient binding. The accessory domain can be either one of the glycine/arginine-rich domains or a second element of the core of the protein that is highly conserved between different species
Epigenetic switch controls social actions
No full text: Mutations in epigenetic factors are associated with autism spectrum disorder (ASD). In this issue of Neuron, Yan et al. (2022) show that the antagonism of ASH1L and PRC2 switches the equilibrium of histone methylation at the ephrin receptor A7 locus; causing decreased EphA7 expression, deficits in synaptic pruning, and ASD-like behaviors
Neurons acetylate their way to migration
No full textThe centrosome is crucial for neuronal migration and polarisation, processes that are disrupted in a number of neurodevelopmental disorders including schizophrenia. Mutation of DISC1, associated with increased risk of schizophrenia and psychiatric illness, has been shown to affect the centrosome, but the mechanisms involved have not been elucidated. In this issue of EMBO Reports, Fukuda and colleagues demonstrate that a DISC1-interacting protein, CAMDI, suppresses the activity of the histone deacetylase HDAC6, thereby promoting centrosome stability and consequently neuronal migration . Loss of CAMDI leads to cortical migration defects and behavioural phenotypes that model autism spectrum disorders and which can be rescued by inhibition of HDAC6. The study provides novel mechanistic insight into centrosome regulation in neurodevelopment
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