Role of RNA Binding Proteins with prion-like domains in muscle and neuromuscular diseases

Picchiarelli, Gina; Dupuis, Luc

doi:10.15698/cst2020.04.217

Cited by 42 publications

(35 citation statements)

References 185 publications

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“…RBPs have been shown to critically regulate multiple events of RNA lifecycle, including transcriptional, splicing, RNA tra cking and sequestration [25]. RBPs also contribute to translational and posttranslational regulation through binding to 3' untranslated regions of mRNAs [26].…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of the functions of RNA binding proteins in clear cell renal cell carcinoma

Hua¹,

Chen

Ge³

et al. 2021

Genomics

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Background: RNA binding proteins (RBPs) dysregulation is involved in the process es of various tumor. However, the roles of RBPs in clear cell renal cell carcinoma (ccRCC) remain poorly understand. Systematic exploration of the roles of RBPs in ccRCC may provide new insights for the treatments of ccRCC. Methods: Expression data of RBPs was obtained from The Cancer Genome Atlas database. The roles of RBPs in ccRCC were systematically investigated using consensus clustering methods. Differentially expressed RBPs between normal and tumor tissues were obtained. Protein-protein interaction (PPI) network was constructed using "STRING" software. The expression levels of hub genes were validated in The Human Protein Atlas (HPA) database and receiver operating characteristic (ROC) curves were used to evaluate diagnostic value. Univariate and Lasso Cox regression and Kaplan-Meier curves were used to screen the most useful prognostic genes. Multivariate Cox regression was performed to construct a risk score model. The e ciency of the model was evaluated using time-dependent ROC and Kaplan-Meier curves, and validated in E-MTAB-3267 set. Results: Two clusters were identi ed based on the expression similarity of RBPs, and the cluster 2 was closely correlated with the malignancy of ccRCC. Several oncogenic pathways, including epithelial mesenchymal transition, G2M checkpoint, KRAS signaling and IL6 JAK STAT3 signaling were enriched in cluster 2. In addition, we obtained 115 differently expressed RBPs in ccRCC, comprising 71 up-regulated and 44 down-regulated ones. Ten hub RBPs with good diagnostic value were obtained from PPI network and validated in HPA database. Ten RBPs were identi ed as survival-related genes and used to construct a risk score model. The model could be used to stratify patients with different prognosis. We found highrisk patients tended to be advanced stage, high grade, high pathological T staging and could be an independent risk factor for overall survival of ccRCC patients. Conclusions: We identi ed ten RBPs with diagnostic value, which might be the potential diagnostic biomarkers for ccRCC. A risk score model was established to stratify patients and could be used as a complementation for clinical factors to guide clinical practice in the future.

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Section: Discussionmentioning

confidence: 99%

Integrated analysis of the functions of RNA binding proteins in clear cell renal cell carcinoma

Hua¹,

Chen

Ge³

et al. 2021

Genomics

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“…Protein aggregates positive for TDP-43 [ 36 , 205 ], neurofilament [ 41 ], FUS [ 87 ], or SOD1 [ 206 ] are observed in the vast majority of ALS patients, with TDP-43 being present in as many as 98% of sporadic and familial cases [ 207 ], meaning that the presence of such aggregates is widely regarded as a hallmark feature of ALS pathology. These deposits can occur in the cytoplasm of neurons [ 208 ] and skeletal muscle [ 99 , 209 ], and their presence is highly suggestive of an imbalance between protein synthesis and degradation pathways ( Figure 2 ).…”

Section: Impaired Protein Homeostasismentioning

confidence: 99%

“…However, a reducing and metal-poor intracellular environment or mutations [ 221 , 222 , 223 , 224 , 225 , 226 , 227 ] can abolish these features and destabilize SOD1, leading to the formation of aggregates and amyloid fibril structures [ 228 , 229 , 230 , 231 ] that can self-propagate in vitro [ 229 , 230 ]. FUS and TDP-43 proteins possess a low complexity domain that presents similarities with yeast prions [ 209 ] and can form large aggregates and amyloid fibril structures [ 209 , 229 , 232 , 233 ]. Interestingly, mutated forms of FUS and TDP-43 can induce the misfolding of wild type forms of FUS and TDP-43, respectively [ 229 ], and have also been shown to induce the misfolding of wild type forms of SOD1 in vitro [ 234 ].…”

Section: Impaired Protein Homeostasismentioning

confidence: 99%

Molecular and Cellular Mechanisms Affected in ALS

Gall

Anakor

Connolly

et al. 2020

JPM

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Amyotrophic lateral sclerosis (ALS) is a terminal late-onset condition characterized by the loss of upper and lower motor neurons. Mutations in more than 30 genes are associated to the disease, but these explain only ~20% of cases. The molecular functions of these genes implicate a wide range of cellular processes in ALS pathology, a cohesive understanding of which may provide clues to common molecular mechanisms across both familial (inherited) and sporadic cases and could be key to the development of effective therapeutic approaches. Here, the different pathways that have been investigated in ALS are summarized, discussing in detail: mitochondrial dysfunction, oxidative stress, axonal transport dysregulation, glutamate excitotoxicity, endosomal and vesicular transport impairment, impaired protein homeostasis, and aberrant RNA metabolism. This review considers the mechanistic roles of ALS-associated genes in pathology, viewed through the prism of shared molecular pathways.

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“…As a result, knock‐in mice expressing mutant FUS suffer from denervation of neuromuscular endplates before motor neuron loss, which is consistent with a “dying‐back” model. Of note, FUS is a member that is structurally similar to the FET protein family consisting of three ALS genes (FUS, EWS, and TAF15), all of which are present in skeletal muscle and mutations that can cause muscle defects involving mitochondrial function (Picchiarelli & Dupuis, 2020). FUS is also an essential component of nuclear paraspeckles and can be found in recently discovered nuclear stress‐induced silencing complex responsible for nuclear transport of small nucleotide sequences, including microRNAs (miRNAs) (Castanotto et al, 2018).…”

Section: Rna Metabolism In Als Skeletal Musclementioning

confidence: 99%

What skeletal muscle has to say in amyotrophic lateral sclerosis: Implications for therapy

Manzano

Toivonen

Moreno-Martínez

et al. 2020

British J Pharmacology

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Amyotrophic lateral sclerosis (ALS) is an adult onset disorder characterized by progressive neuromuscular junction (NMJ) dismantling and degeneration of motor neurons leading to atrophy and paralysis of voluntary muscles responsible for motion and breathing. Except for a minority of patients harbouring genetic mutations, the origin of most ALS cases remains elusive. Peripheral tissues, and particularly skeletal muscle, have lately demonstrated an active contribution to disease pathology attracting a growing interest for these tissues as therapeutic targets in ALS. In this sense, molecular mechanisms essential for cell and tissue homeostasis have been shown to be deregulated in the disease. These include muscle metabolism and mitochondrial activity, RNA processing, tissue‐resident stem cell function responsible for muscle regeneration, and proteostasis that regulates muscle mass in adulthood. This review aims to compile scientific evidence that demonstrates the role of skeletal muscle in ALS pathology and serves as reference for development of novel therapeutic strategies targeting this tissue to delay disease onset and progression. LINKED ARTICLES This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc

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Role of RNA Binding Proteins with prion-like domains in muscle and neuromuscular diseases

Cited by 42 publications

References 185 publications

Integrated analysis of the functions of RNA binding proteins in clear cell renal cell carcinoma

Integrated analysis of the functions of RNA binding proteins in clear cell renal cell carcinoma

Molecular and Cellular Mechanisms Affected in ALS

What skeletal muscle has to say in amyotrophic lateral sclerosis: Implications for therapy

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