The sedimentation distribution of proteins along the sucrose gradient is expressed as percentage in each fraction considering as 100% the sum of all fractions. RPL26 and RPS6 were used as sedimentation controls for the large and small ribosomal subunits, respectively. d-e, Polysomal profiling and co-sedimentation profiles of lysates obtained from control brain before ( d) and after ( e) RNAse I treatment. The experiment was performed as in Fig.1e and was repeated independently 2 times with similar results. c, Western blot analysis on P7 cytoplasmic lysates from control P7 spinal cord. The data represent the average ± SEM among n=3 independent experiments. The unspecific binding was obtained as in panel ( a). b, Saturation curve obtained using experiments as in Fig.1. The presence of SMN in the pellet was determined by western blot and densitometric analysis. The experiment was performed as in Fig.1c, in the absence of ribosomes. Thus, SMN plays a crucial role in the regulation of ribosome fluxes along mRNAs encoding proteins that are relevant to SMA pathogenesis.Ī, Samples were ultracentrifuged to evaluate the aspecific sedimentation of SMN. Loss of SMN induces ribosome depletion, especially at the beginning of the coding sequence of SMN-specific mRNAs, leading to impairment of proteins that are involved in motor neuron function and stability, including acetylcholinesterase. These SMN-specific mRNAs are associated with neurogenesis, lipid metabolism, ubiquitination, chromatin regulation and translation. SMN-primed ribosomes are preferentially positioned within the first five codons of a set of mRNAs that are enriched for translational enhancer sequences in the 5' untranslated region (UTR) and rare codons at the beginning of their coding sequence. Here, we demonstrate that survival motor neuron (SMN) protein-the loss of which causes the neuromuscular disease spinal muscular atrophy (SMA)-binds to ribosomes and that this interaction is tissue-dependent. ![]() The contribution of ribosome heterogeneity and ribosome-associated proteins to the molecular control of proteomes in health and disease remains unclear.
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