The SARS-CoV-2 targeted human RNA binding proteins network biology to investigate COVID-19 associated manifestations

Prasad, Kartikay; Gour, Pratibha; Raghuvanshi, Saurabh; Kumar, Vijay

doi:10.1016/j.ijbiomac.2022.07.200

Cited by 5 publications

(4 citation statements)

References 110 publications

(112 reference statements)

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“…Even though few potential drugs have been found to target FUBP1 and RAB2A, using RNA-binding proteins to treat COVID-19 is still promising. Researchers have found pioglitazone and lapatinib as potential drugs since pioglitazone decreases the expression of RPS3, eIF4B, and RPS10, while lapatinib decreases the expression of EEF1A1, EIF5A, and RPS10 RBPs 78 . Another study investigated drugs targeting the interacting proteins of SARS-CoV-2-related RBPs and identified Doxorubicin and Topotecan as possible drugs targeting protein interactome of RBPs 79 , providing another way to use RBPs in the treatment of COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Integration of risk variants from GWAS with SARS-CoV-2 RNA interactome prioritizes FUBP1 and RAB2A as risk genes for COVID-19

Shi,

Chen,

Pan

et al. 2023

Sci Rep

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The role of host genetic factors in COVID-19 outcomes remains unclear despite various genome-wide association studies (GWAS). We annotate all significant variants and those variants in high LD (R2 > 0.8) from the COVID-19 host genetics initiative (HGI) and identify risk genes by recognizing genes intolerant nonsynonymous mutations in coding regions and genes associated with cis-expression quantitative trait loci (cis-eQTL) in non-coding regions. These genes are enriched in the immune response pathway and viral life cycle. It has been found that host RNA binding proteins (RBPs) participate in different phases of the SARS-CoV-2 life cycle. We collect 503 RBPs that interact with SARS-CoV-2 RNA concluded from in vitro studies. Combining risk genes from the HGI with RBPs, we identify two COVID-19 risk loci that regulate the expression levels of FUBP1 and RAB2A in the lung. Due to the risk allele, COVID-19 patients show downregulation of FUBP1 and upregulation of RAB2A. Using single-cell RNA sequencing data, we show that FUBP1 and RAB2A are expressed in SARS-CoV-2-infected upper respiratory tract epithelial cells. We further identify NC_000001.11:g.77984833C>A and NC_000008.11:g.60559280T>C as functional variants by surveying allele-specific transcription factor sites and cis-regulatory elements and performing motif analysis. To sum up, our research, which associates human genetics with expression levels of RBPs, identifies FUBP1 and RAB2A as two risk genes for COVID-19 and reveals the anti-viral role of FUBP1 and the pro-viral role of RAB2A in the infection of SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

Integration of risk variants from GWAS with SARS-CoV-2 RNA interactome prioritizes FUBP1 and RAB2A as risk genes for COVID-19

Shi,

Chen,

Pan

et al. 2023

Sci Rep

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“…RBPs are the primary agents through which RNA regulates cellular states. It is also noteworthy that RBPs represent important drug-targeted sites (Prasad et al 2022). Traditionally, the characterization of protein binding has often relied on sequence information.…”

Section: Rna Binding Proteinmentioning

confidence: 99%

RNA structure: implications in viral infections and neurodegenerative diseases

Lu,

Tang,

Yin

et al. 2024

Adv. Biotechnol.

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RNA is an intermediary between DNA and protein, a catalyzer of biochemical reactions, and a regulator of genes and transcripts. RNA structures are essential for complicated functions. Recent years have witnessed rapid advancements in RNA secondary structure probing techniques. These technological strides provided comprehensive insights into RNA structures, which significantly contributed to our understanding of diverse cellular regulatory processes, including gene regulation, epigenetic regulation, and post-transactional regulation. Meanwhile, they have facilitated the creation of therapeutic tools for tackling human diseases. Despite their therapeutic applications, RNA structure probing methods also offer a promising avenue for exploring the mechanisms of human diseases, potentially providing the key to overcoming existing research constraints and obtaining the in-depth information necessary for a deeper understanding of disease mechanisms.

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“…SARS‐CoV‐2 can also disrupt neuronal RNA metabolism at multiple levels, including by the recruitment of host RNA‐binding proteins (RBPs) into its interactome. By examining the network of RBPs that interact directly with the SARS‐CoV‐2 transcript and comparing these to published gene databases for neurological disorders, a common pool of 9 RBPs that interact with the SARS‐CoV‐2 transcript and are associated with cancer and neurological disorders has been characterized (Prasad et al, 2022; Schmidt et al, 2021). Among the most highly linked neurological dysfunctions were dementia, depressive disorder, and anxiety.…”

Section: Putative Mechanisms Of the Induction Of Neurodegenerationmentioning

confidence: 99%

SARS‐CoV‐2, aging, and Post‐COVID‐19 neurodegeneration

Strong

2022

Journal of Neurochemistry

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As the world continues to experience the effects of SARS‐CoV‐2, there is evidence to suggest that the sequelae of viral infection (the post‐COVID‐19 condition; PCC) at both an individual and population level will be significant and long‐lasting. The history of pandemics or epidemics in the last 100 years caused by members of the RNA virus family, of which coronaviruses are a member, provides ample evidence of the acute neurological effects. However, except for the H1N1 influenza pandemic of 1918/1919 (the Spanish flu) with its associated encephalitis lethargica, there is little information on long‐term neurological sequelae. COVID‐19 is the first pandemic that has occurred in a setting of an aging population, especially in several high‐income countries. Its survivors are at the greatest risk for developing neurodegenerative conditions as they age, rendering the current pandemic a unique paradigm not previously witnessed. The SARS‐CoV‐2 virus, among the largest of the RNA viruses, is a single‐stranded RNA that encodes for 29 proteins that include the spike protein that contains the key domains required for ACE2 binding, and a complex array of nonstructural proteins (NSPs) and accessory proteins that ensure the escape of the virus from the innate immune response, allowing for its efficient replication, translation, and exocytosis as a fully functional virion. Increasingly, these proteins are also recognized as potentially contributing to biochemical and molecular processes underlying neurodegeneration. In addition to directly being taken up by brain endothelium, the virus or key protein constituents can be transported to neurons, astrocytes, and microglia by extracellular vesicles and can accelerate pathological fibril formation. The SARS‐CoV‐2 nucleocapsid protein is intrinsically disordered and can participate in liquid condensate formation, including as pathological heteropolymers with neurodegenerative disease‐associated RNA‐binding proteins such as TDP‐43, FUS, and hnRNP1A. As the SARS‐CoV‐2 virus continues to mutate under the immune pressure exerted by highly efficacious vaccines, it is evolving into a virus with greater transmissibility but less severity compared with the original strain. The potential of its lingering impact on the nervous system thus has the potential to represent an ongoing legacy of an even greater global health challenge than acute infection.

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The SARS-CoV-2 targeted human RNA binding proteins network biology to investigate COVID-19 associated manifestations

Cited by 5 publications

References 110 publications

Integration of risk variants from GWAS with SARS-CoV-2 RNA interactome prioritizes FUBP1 and RAB2A as risk genes for COVID-19

Integration of risk variants from GWAS with SARS-CoV-2 RNA interactome prioritizes FUBP1 and RAB2A as risk genes for COVID-19

RNA structure: implications in viral infections and neurodegenerative diseases

SARS‐CoV‐2, aging, and Post‐COVID‐19 neurodegeneration

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