Primate-specific miR-603 is implicated in the risk and pathogenesis of Alzheimer's disease

Zhang, Chi; Lu, Jie; Liu, Bing; Cui, Qinghua; Wang, Yun

doi:10.18632/aging.100887

Cited by 32 publications

(18 citation statements)

References 57 publications

(18 reference statements)

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“…Ribosome profiling sequencing (RPF-Seq) and RNA-Seq libraries treated with specific miRNA overexpression, 12 experimental conditions in total (Supplementary Tables 5 – 7 ), were retrieved from Eichhorn et al 36 , Nam et al 11 , Pellegrino et al 37 , Zhang et al 38 . To identify positive/negative miRNA interactions, a ±0.5 log2 fold-change threshold was applied to genes presenting > 10 RPKM expression.…”

Section: Methodsmentioning

confidence: 99%

microCLIP super learning framework uncovers functional transcriptome-wide miRNA interactions

et al. 2018

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Argonaute crosslinking and immunoprecipitation (CLIP) experiments are the most widely used high-throughput methodologies for miRNA targetome characterization. The analysis of Photoactivatable Ribonucleoside-Enhanced (PAR) CLIP methodology focuses on sequence clusters containing T-to-C conversions. Here, we demonstrate for the first time that the non-T-to-C clusters, frequently observed in PAR-CLIP experiments, exhibit functional miRNA-binding events and strong RNA accessibility. This discovery is based on the analysis of an extensive compendium of bona fide miRNA-binding events, and is further supported by numerous miRNA perturbation experiments and structural sequencing data. The incorporation of these previously neglected clusters yields an average of 14% increase in miRNA-target interactions per PAR-CLIP library. Our findings are integrated in microCLIP (www.microrna.gr/microCLIP), a cutting-edge framework that combines deep learning classifiers under a super learning scheme. The increased performance of microCLIP in CLIP-Seq-guided detection of miRNA interactions, uncovers previously elusive regulatory events and miRNA-controlled pathways.

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Section: Methodsmentioning

confidence: 99%

microCLIP super learning framework uncovers functional transcriptome-wide miRNA interactions

et al. 2018

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“…Compared with miR2Disease, NSDNA also includes data regarding mutations in ncRNA and their association with NSDs. For example, in the NSDNA database, we also found that a SNP (rs11014002) located in miR-603 precursor exhibits a protective effect toward Alzheimer disease risk (31). Moreover, miR2Disease has not been updated since 2009.…”

Section: Discussionmentioning

confidence: 98%

NSDNA: a manually curated database of experimentally supported ncRNAs associated with nervous system diseases

et al. 2016

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The Nervous System Disease NcRNAome Atlas (NSDNA) (http://www.bio-bigdata.net/nsdna/) is a manually curated database that provides comprehensive experimentally supported associations about nervous system diseases (NSDs) and noncoding RNAs (ncRNAs). NSDs represent a common group of disorders, some of which are characterized by high morbidity and disabilities. The pathogenesis of NSDs at the molecular level remains poorly understood. ncRNAs are a large family of functionally important RNA molecules. Increasing evidence shows that diverse ncRNAs play a critical role in various NSDs. Mining and summarizing NSD–ncRNA association data can help researchers discover useful information. Hence, we developed an NSDNA database that documents 24 713 associations between 142 NSDs and 8593 ncRNAs in 11 species, curated from more than 1300 articles. This database provides a user-friendly interface for browsing and searching and allows for data downloading flexibility. In addition, NSDNA offers a submission page for researchers to submit novel NSD–ncRNA associations. It represents an extremely useful and valuable resource for researchers who seek to understand the functions and molecular mechanisms of ncRNA involved in NSDs.

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“…Other neurodegenerative disease genes such as MTMR2, in which pathogenic variants cause Charcot-Marie-Tooth disease type 4B, an autosomal recessive demyelinating neuropathy [71], and NGFR, previously suggested to be involved in AD [72], were found to be tissue co-expression partners of TECPR2. Furthermore, TECPR2 was found to have coevolved with genes implicated in neurodegenerative disorders such as ATXN1 [44] and KIAA1217 [73].…”

Section: Discussionmentioning

confidence: 99%

Integrative functional analyses of the neurodegenerative disease-associated TECPR2 gene reveal its diverse roles

Shalev¹,

Somekh²,

Eran³

2020

Preprint

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BackgroundLoss of tectonin β-propeller repeat-containing 2 (TECPR2) function has been implicated in an array of neurodegenerative disorders, yet its physiological function remains largely unknown. Understanding TECPR2 function is essential for developing much needed precision therapeutics for TECPR2-related diseases. MethodsWe leveraged the considerable amounts of functional data to obtain a comprehensive perspective of the role of TECPR2 in health and disease. We integrated expression patterns, population variation, phylogenetic profiling, protein-protein interactions, and regulatory network data for a minimally biased multimodal functional analysis. Genes and proteins linked to TECPR2 via multiple lines of evidence were subject to functional enrichment analyses to identify molecular mechanisms involving TECPR2.ResultsTECPR2 was found to be part of a tight neurodevelopmental gene expression program that includes KIF1A, ATXN1, TOM1L2, and FA2H, all implicated in neurological diseases. Functional enrichment analyses of TECPR2-related genes converged on a role in late autophagy and ribosomal processes. Large-scale population variation data demonstrated that this role is nonredundant. ConclusionsTECPR2 might serve as an indicator for the energy balance between protein synthesis and autophagy, and a marker for diseases associated with their imbalance, such as Alzheimer’s disease, Huntington’s disease, and various cancers. Our work further suggests that TECPR2 plays a role as a synaptic proteostasis regulator during synaptogenesis, highlighting its importance in developing neurons. By advancing our understanding of TECPR2 function, this work provides an essential stepping stone towards the development of precision diagnostics and targeted treatment options for TECPR2-related disorders.

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Primate-specific miR-603 is implicated in the risk and pathogenesis of Alzheimer's disease

Cited by 32 publications

References 57 publications

microCLIP super learning framework uncovers functional transcriptome-wide miRNA interactions

microCLIP super learning framework uncovers functional transcriptome-wide miRNA interactions

NSDNA: a manually curated database of experimentally supported ncRNAs associated with nervous system diseases

Integrative functional analyses of the neurodegenerative disease-associated TECPR2 gene reveal its diverse roles

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Primate-specific miR-603 is implicated in the risk and pathogenesis of Alzheimer's disease

Cited by 32 publications

References 57 publications

microCLIP super learning framework uncovers functional transcriptome-wide miRNA interactions

microCLIP super learning framework uncovers functional transcriptome-wide miRNA interactions

NSDNA: a manually curated database of experimentally supported ncRNAs associated with nervous system diseases

Integrative functional analyses of the neurodegenerative disease-associated&nbsp;TECPR2&nbsp;gene reveal its diverse roles

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Integrative functional analyses of the neurodegenerative disease-associated TECPR2 gene reveal its diverse roles