Activation of Hypoxia-Inducible Factor Signaling Modulates the RNA Protein Interactome in Caenorhabditis elegans

Esmaillie, Reza; Ignarski, Michael; Bohl, Katrin; Krüger, Tim; Ahmad, Daniyal; Seufert, Lisa; Schermer, Bernhard; Benzing, Thomas; Fabretti, Francesca

doi:10.1016/j.isci.2019.11.039

Cited by 8 publications

(5 citation statements)

References 57 publications

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“…More recent methods using phenol-chloroform extraction ( 16–18 ) or RNase digestion to detect RNA-dependent proteins like R-DeeP or DIF-FRAC ( 19–21 ) were developed. These different strategies were applied to many species, including Homo sapiens ( 7 , 8 , 22–24 ), Mus musculus ( 9 , 11 , 15 , 20 , 25 ), Drosophila melanogaster ( 10 , 26 ), Caenorhabditis elegans ( 27 , 28 ), Saccharomyces cerevisiae ( 22 , 27 , 29 ), Escherichia coli ( 17 , 29 ) and others. They represent valuable and complementary datasets to our understanding of RBPs, their functions and relation to diseases.…”

Section: Introductionmentioning

confidence: 99%

RBP2GO: a comprehensive pan-species database on RNA-binding proteins, their interactions and functions

Caudron-Herger

Jansen

Wassmer

et al. 2020

Nucleic Acids Research

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RNA–protein complexes have emerged as central players in numerous key cellular processes with significant relevance in health and disease. To further deepen our knowledge of RNA-binding proteins (RBPs), multiple proteome-wide strategies have been developed to identify RBPs in different species leading to a large number of studies contributing experimentally identified as well as predicted RBP candidate catalogs. However, the rapid evolution of the field led to an accumulation of isolated datasets, hampering the access and comparison of their valuable content. Moreover, tools to link RBPs to cellular pathways and functions were lacking. Here, to facilitate the efficient screening of the RBP resources, we provide RBP2GO (https://RBP2GO.DKFZ.de), a comprehensive database of all currently available proteome-wide datasets for RBPs across 13 species from 53 studies including 105 datasets identifying altogether 22 552 RBP candidates. These are combined with the information on RBP interaction partners and on the related biological processes, molecular functions and cellular compartments. RBP2GO offers a user-friendly web interface with an RBP scoring system and powerful advanced search tools allowing forward and reverse searches connecting functions and RBPs to stimulate new research directions.

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Section: Introductionmentioning

confidence: 99%

RBP2GO: a comprehensive pan-species database on RNA-binding proteins, their interactions and functions

Caudron-Herger

Jansen

Wassmer

et al. 2020

Nucleic Acids Research

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“…Comparative RIC technologies have been previously used to understand the dynamic RBPome under a variety of conditions and organisms, either combined with label-free mass spectrometry, as in our study, or with SILAC or TMT labeling (31,36,50,(70)(71)(72)(73)(74)(75)(76). To our knowledge, however, it has not been used to reveal RBPs important for metastatic progression.…”

Section: Discussionmentioning

confidence: 99%

Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis

Mestre-Farràs

Guerrero

Bley

et al. 2022

Nucleic Acids Research

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RNA-binding proteins (RBPs) have been relatively overlooked in cancer research despite their contribution to virtually every cancer hallmark. Here, we use RNA interactome capture (RIC) to characterize the melanoma RBPome and uncover novel RBPs involved in melanoma progression. Comparison of RIC profiles of a non-tumoral versus a metastatic cell line revealed prevalent changes in RNA-binding capacities that were not associated with changes in RBP levels. Extensive functional validation of a selected group of 24 RBPs using five different in vitro assays unveiled unanticipated roles of RBPs in melanoma malignancy. As proof-of-principle we focused on PDIA6, an ER-lumen chaperone that displayed a novel RNA-binding activity. We show that PDIA6 is involved in metastatic progression, map its RNA-binding domain, and find that RNA binding is required for PDIA6 tumorigenic properties. These results exemplify how RIC technologies can be harnessed to uncover novel vulnerabilities of cancer cells.

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“…We aimed to determine the transcriptional targets of HIF-1 and their mechanisms of action underlying protection against heat stress and APOE4. Proteomic and transcriptomic studies have identified many genes differentially regulated in vhl-1 mutants [49][50][51] . We used quantitative RT-PCR (qRT-PCR) and GFP reporters to validate many of these targets based on their dramatic up-regulation in vhl-1 mutants grown at 28 o C, under which condition HIF-1 is both stabilized and activated in target gene transcriptional transactivation (Figure 6A).…”

Section: Transcriptional Targets Of Hif-1 Mediating Effects Of Vhl-1 ...mentioning

confidence: 99%

Suppressing APOE4-induced mortality and cellular damage by targeting VHL

Jiang,

Cao,

Xue

et al. 2024

Preprint

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SUMMARYMortality rate increases with age and can accelerate upon extrinsic or intrinsic damage to individuals. Identifying factors and mechanisms that curb population mortality rate has wide-ranging implications. Here, we show that targeting the VHL-1 (Von Hippel– Lindau) protein suppressesC. elegansmortality caused by distinct factors, including elevated reactive oxygen species, temperature, andAPOE4, the genetic variant that confers high risks of neurodegeneration in Alzheimer’s diseases and all-cause mortality in humans. These mortality factors are of different physical-chemical nature, yet result in similar cellular dysfunction and damage that are suppressed by deleting VHL-1.Stabilized HIF-1 (hypoxia inducible factor), a transcription factor normally targeted for degradation by VHL-1, recapitulates the protective effects of deleting VHL-1. HIF-1 orchestrates a genetic program that defends against mitochondrial abnormalities, excess oxidative stress, cellular proteostasis dysregulation, and endo-lysosomal rupture, all events that lead to mortality. Genetic inhibition ofVhlalso alleviates cerebral vascular injury and synaptic lesions inAPOE4mice, supporting an evolutionarily conserved mechanism. Collectively, we identify the VHL-HIF axis as a potent modifier of APOE4 and propose that targeting VHL-HIF in non-proliferative animal tissues may suppress tissue injuries and mortality by broadly curbing cellular damage.

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Activation of Hypoxia-Inducible Factor Signaling Modulates the RNA Protein Interactome in Caenorhabditis elegans

Cited by 8 publications

References 57 publications

RBP2GO: a comprehensive pan-species database on RNA-binding proteins, their interactions and functions

RBP2GO: a comprehensive pan-species database on RNA-binding proteins, their interactions and functions

Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis

Suppressing APOE4-induced mortality and cellular damage by targeting VHL

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