The role of the protein–RNA recognition code in neurodegeneration

Nahálka, Jozef

doi:10.1007/s00018-019-03096-3

Cited by 23 publications

(26 citation statements)

References 103 publications

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“…A total of 1542 RBPs have been identified by highthroughput screening in human cells, representing 7.5% of all protein coding genes (Gerstberger et al, 2014). These RBPs affect post-transcriptional events in cells and modulate cell physiology, and are therefore involved in multiple biological processes including RNA splicing, mRNA stability, export to the cytoplasm, localization, and protein translation (Masuda and Kuwano, 2019;Nahalka, 2019). Given that RPBs perform various critical functions in post-transcriptional events, it is unsurprising that alterations in RBPs are closely related to the initiation and progression of many human diseases.…”

Section: Introductionmentioning

confidence: 99%

Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma

Xue

Gao

et al. 2020

Front. Genet.

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Lung cancer is the leading cause of cancer-related deaths worldwide. Dysregulation of RNA binding proteins (RBPs) has been found in a variety of cancers and is related to oncogenesis and progression. However, the functions of RBPs in lung squamous cell carcinoma (LUSC) remain unclear. In this study, we obtained gene expression data and corresponding clinical information for LUSC from The Cancer Genome Atlas (TCGA) database, identified aberrantly expressed RBPs between tumors and normal tissue, and conducted a series of bioinformatics analyses to explore the expression and prognostic value of these RBPs. A total of 300 aberrantly expressed RBPs were obtained, comprising 59 downregulated and 241 upregulated RBPs. Functional enrichment analysis indicated that the differentially expressed RBPs were mainly associated with mRNA metabolic processes, RNA processing, RNA modification, regulation of translation, the TGF-beta signaling pathway, and the Toll-like receptor signaling pathway. Nine RBP genes (A1CF, EIF2B5, LSM1, LSM7, MBNL2, RSRC1, TRMU, TTF2, and ZCCHC5) were identified as prognosis-associated hub genes by univariate, least absolute shrinkage and selection operator (LASSO), Kaplan-Meier survival, and multivariate Cox regression analyses, and were used to construct the prognostic model. Further analysis demonstrated that high risk scores for patients were significantly related to poor overall survival according to the model. The area under the time-dependent receiver operator characteristic curve of the prognostic model was 0.712 at 3 years and 0.696 at 5 years. We also developed a nomogram based on nine RBP genes, with internal validation in the TCGA cohort, which showed a favorable predictive efficacy for prognosis in LUSC. Our results provide novel insights into the pathogenesis of LUSC. The nine-RBP gene signature showed predictive value for LUSC prognosis, with potential applications in clinical decision-making and individualized treatment.

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Section: Introductionmentioning

confidence: 99%

Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma

Xue

Gao

et al. 2020

Front. Genet.

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“…Interestingly, Jozef Nahalka (2019) [ 50 ] investigated an innovative, yet controversial concept of “protein-RNA recognition code” in the context of several neurodegenerative diseases (AD, HD, PD, ALS) and prion disorder. Essentially, the code is based on the idea of “reverse translating” an amino acid sequence or motif from a chosen protein, thus generating a nucleotide sequence that supposedly interacts with that polypeptide.…”

Section: Interplay Between Mirnas and Prions In Diseasementioning

confidence: 99%

MicroRNAs in Prion Diseases—From Molecular Mechanisms to Insights in Translational Medicine

Contiliani

Ribeiro

Moraes

et al. 2021

Cells

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MicroRNAs (miRNAs) are small non-coding RNA molecules able to post-transcriptionally regulate gene expression via base-pairing with partially complementary sequences of target transcripts. Prion diseases comprise a singular group of neurodegenerative conditions caused by endogenous, misfolded pathogenic (prion) proteins, associated with molecular aggregates. In humans, classical prion diseases include Creutzfeldt–Jakob disease, fatal familial insomnia, Gerstmann–Sträussler–Scheinker syndrome, and kuru. The aim of this review is to present the connections between miRNAs and prions, exploring how the interaction of both molecular actors may help understand the susceptibility, onset, progression, and pathological findings typical of such disorders, as well as the interface with some prion-like disorders, such as Alzheimer’s. Additionally, due to the inter-regulation of prions and miRNAs in health and disease, potential biomarkers for non-invasive miRNA-based diagnostics, as well as possible miRNA-based therapies to restore the levels of deregulated miRNAs on prion diseases, are also discussed. Since a cure or effective treatment for prion disorders still pose challenges, miRNA-based therapies emerge as an interesting alternative strategy to tackle such defying medical conditions.

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“…HnRNP H and hnRNP F were also found to co-localize with GGGGCC expansion foci in immunoprecipitation studies [138] and western blot analyses [139] respectively. It has been recently suggested that a GGA-rich sequence on hnRNP H may account for its affinity to the GGGGCC expansion repeats and its sequestration in ALS and FTD [140]. HnRNP sequestration by G quadruplexes in the expansion repeats in ALS and FTD suggests that hnRNP implication may be in part responsible for the toxicity incurred by C9orf72 mutations as important RNA processes such as splicing are compromised [141].…”

Section: Amyotrophic Lateral Sclerosis and Frontotemporal Dementiamentioning

confidence: 99%

Heterogeneous Nuclear Ribonucleoproteins: Implications in Neurological Diseases

et al. 2020

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Heterogenous nuclear ribonucleoproteins (hnRNPs) are a complex and functionally diverse family of RNA binding proteins with multifarious roles. They are involved, directly or indirectly, in alternative splicing, transcriptional and translational regulation, stress granule formation, cell cycle regulation, and axonal transport. It is unsurprising, given their heavy involvement in maintaining functional integrity of the cell, that their dysfunction has neurological implications. However, compared to their more established roles in cancer, the evidence of hnRNP implication in neurological diseases is still in its infancy. This review aims to consolidate the evidences for hnRNP involvement in neurological diseases, with a focus on spinal muscular atrophy (SMA), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), multiple sclerosis (MS), congenital myasthenic syndrome (CMS), and fragile X-associated tremor/ataxia syndrome (FXTAS). Understanding more about hnRNP involvement in neurological diseases can further elucidate the pathomechanisms involved in these diseases and perhaps guide future therapeutic advances.

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The role of the protein–RNA recognition code in neurodegeneration

Cited by 23 publications

References 103 publications

Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma

Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma

MicroRNAs in Prion Diseases—From Molecular Mechanisms to Insights in Translational Medicine

Heterogeneous Nuclear Ribonucleoproteins: Implications in Neurological Diseases

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