hnRNP A/B Proteins: An Encyclopedic Assessment of Their Roles in Homeostasis and Disease

Thibault, Patricia A.; Kalyaanamoorthy, Subha; Clarke, Joseph P.; Salapa, Hannah E.; Levin, Michael C.

doi:10.3390/biology10080712

Cited by 29 publications

(33 citation statements)

References 324 publications

(529 reference statements)

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“…The family of RNA binding proteins (RBPs), known as heterogeneous nuclear ribonucleoproteins (hnRNPs), represent one of the most complex and diverse groups of RBPs and are among one of the most widely expressed proteins in the nucleus ( Bekenstein and Soreq, 2013 ; Jean-Philippe et al, 2013 ; Thibault et al, 2021 ). HnRNP A1 is an abundant member of the A/B subfamily of hnRNPs that constitutes nearly 60% of the total protein mass of the hnRNP particles ( Bekenstein and Soreq, 2013 ) and plays a vital role in gene expression through controlling mRNA stability, regulation of translation, and in processing nascent transcripts through splicing ( Tavanez et al, 2012 ; Geuens et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Knock-Down of Heterogeneous Nuclear Ribonucleoprotein A1 Results in Neurite Damage, Altered Stress Granule Biology, and Cellular Toxicity in Differentiated Neuronal Cells

Anees

Salapa

Thibault

et al. 2021

eNeuro

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Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an RNA binding protein (RBP) that is localized within neurons and plays crucial roles in RNA metabolism. Its importance in neuronal functioning is underscored from the study of its pathogenic features in many neurodegenerative diseases where neuronal hnRNP A1 is mislocalized from the nucleus to the cytoplasm resulting in loss of hnRNP A1 function. Here, we model hnRNP A1 loss-of-function by siRNA mediated knockdown in differentiated Neuro-2a cells. Through RNA sequencing (RNA-seq) followed by gene ontology (GO) analyses, we show that hnRNP A1 is involved in important biological processes, including RNA metabolism, neuronal function, neuronal morphology, neuronal viability, and stress granule (SG) formation. We further confirmed several of these roles by showing that hnRNP A1 knockdown results in a reduction of neurite outgrowth, increase in cell cytotoxicity and changes in SG formation. In summary, these findings indicate that hnRNP A1 loss-of-function contributes to neuronal dysfunction and cell death and implicates hnRNP A1 dysfunction in the pathogenesis of neurodegenerative diseases. Significance StatementHnRNP A1 plays a biologically important role in controlling gene expression and maintaining proper cellular functioning in neurons. Previous research has shown that many neurodegenerative diseases exhibit pathogenic features of hnRNP A1 dysfunction, whereby it is mislocalized from its homeostatic nuclear location to the cytoplasm resulting in loss of proper functioning. Here, we model hnRNP A1 loss-of-function in differentiated neuronal cells and show that it contributes to neuronal dysfunction and cell death. These 3 data are important because it underscores the importance of loss-of-function models and implicates hnRNP A1 dysfunction in the pathogenesis of neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

Knock-Down of Heterogeneous Nuclear Ribonucleoprotein A1 Results in Neurite Damage, Altered Stress Granule Biology, and Cellular Toxicity in Differentiated Neuronal Cells

Anees

Salapa

Thibault

et al. 2021

eNeuro

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“…To sum up, hnRNPA/B is a subgroup of proteins sharing similar structures consisting of two RRM and a glycine-rich domain that further encompasses an RGG box, an M9-NLS and a core prion-like domain (PrLD) [ 6 , 16 ]. HnRNPA/B is predominantly localized in the eukaryotic nucleus and can accompany RNA transcripts into the cytoplasm in cooperation with the nuclear pore complex (NPC) [ 17 ].…”

Section: Profiles Of Hnrnpa/b: Structure and Intracellular Localizationmentioning

confidence: 99%

“…Recently, the biological value of hnRNPA/B has been widely discussed and highly valued. HnRNPA/B members share similar biogenesis and penetrate extensively and deeply into all levels of cellular RNA metabolism, participating in DNA binding, RNA splicing and trafficking, and mRNA translation and stability [ 6 ]. Although the structural characterization of hnRNPA/B and its role in RNA homeostasis have been studied and summarized in detail [ 7 ], the different biological functions of its four isoforms in human cancers are vital topics that cannot be overlooked.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous nuclear ribonucleoprotein A/B: an emerging group of cancer biomarkers and therapeutic targets

Wang

et al. 2022

Cell Death Discov.

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Heterogeneous nuclear ribonucleoprotein A/B (hnRNPA/B) is one of the core members of the RNA binding protein (RBP) hnRNPs family, including four main subtypes, A0, A1, A2/B1 and A3, which share the similar structure and functions. With the advance in understanding the molecular biology of hnRNPA/B, it has been gradually revealed that hnRNPA/B plays a critical role in almost the entire steps of RNA life cycle and its aberrant expression and mutation have important effects on the occurrence and progression of various cancers. This review focuses on the clinical significance of hnRNPA/B in various cancers and systematically summarizes its biological function and molecular mechanisms.

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“…HnRNPs constitute a family of cellular RNA-binding proteins involved in processing pre-mRNA as well as in mRNA translation, trafficking and stability [132,133]. Several studies have ascribed relevant functions to hnRNPs in diverse viral infections including influenza and human immunodeficiency virus (HIV), among others [134][135][136].…”

Section: Host Heterogeneous Nuclear Ribonucleoproteins (Hnrnps) Are S...mentioning

confidence: 99%

The Virus–Host Interplay in Junín Mammarenavirus Infection

Gallo

López

Loureiro

2022

Viruses

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Junín virus (JUNV) belongs to the Arenaviridae family and is the causative agent of Argentine hemorrhagic fever (AHF), a severe human disease endemic to agricultural areas in Argentina. At this moment, there are no effective antiviral therapeutics to battle pathogenic arenaviruses. Cumulative reports from recent years have widely provided information on cellular factors playing key roles during JUNV infection. In this review, we summarize research on host molecular determinants that intervene in the different stages of the viral life cycle: viral entry, replication, assembly and budding. Alongside, we describe JUNV tight interplay with the innate immune system. We also review the development of different reverse genetics systems and their use as tools to study JUNV biology and its close teamwork with the host. Elucidating relevant interactions of the virus with the host cell machinery is highly necessary to better understand the mechanistic basis beyond virus multiplication, disease pathogenesis and viral subversion of the immune response. Altogether, this knowledge becomes essential for identifying potential targets for the rational design of novel antiviral treatments to combat JUNV as well as other pathogenic arenaviruses.

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hnRNP A/B Proteins: An Encyclopedic Assessment of Their Roles in Homeostasis and Disease

Cited by 29 publications

References 324 publications

Knock-Down of Heterogeneous Nuclear Ribonucleoprotein A1 Results in Neurite Damage, Altered Stress Granule Biology, and Cellular Toxicity in Differentiated Neuronal Cells

Knock-Down of Heterogeneous Nuclear Ribonucleoprotein A1 Results in Neurite Damage, Altered Stress Granule Biology, and Cellular Toxicity in Differentiated Neuronal Cells

Heterogeneous nuclear ribonucleoprotein A/B: an emerging group of cancer biomarkers and therapeutic targets

The Virus–Host Interplay in Junín Mammarenavirus Infection

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