RNA decay machinery safeguards immune cell development and immunological responses

Akiyama, Taishin; Suzuki, Toru; Yamamoto, Tadashi

doi:10.1016/j.it.2021.03.008

Cited by 9 publications

(8 citation statements)

References 120 publications

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“…The Hhub WASHC5 codes for strumpellin, a protein involved in endosomal fission 45 that was shown to interact directly with SARS-CoV-2 46 . The Hhub CNOT8 encodes the CNOT8 catalytic subunit of the CCR4-NOT complex, which is required for selective mRNA degradation (mRNA surveillance) and for preventing excessive inflammatory responses 47 . The eHub PSMD10 codes for gankyrin and promotes autophagy 48 , a crucial innate immune response against infection.…”

Section: Resultsmentioning

confidence: 99%

Blood leukocyte transcriptional modules and differentially expressed genes associated with disease severity and age in COVID-19 patients

Bando

Bertonha

Vieira

et al. 2023

Sci Rep

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Since the molecular mechanisms determining COVID-19 severity are not yet well understood, there is a demand for biomarkers derived from comparative transcriptome analyses of mild and severe cases, combined with patients’ clinico-demographic and laboratory data. Here the transcriptomic response of human leukocytes to SARS-CoV-2 infection was investigated by focusing on the differences between mild and severe cases and between age subgroups (younger and older adults). Three transcriptional modules correlated with these traits were functionally characterized, as well as 23 differentially expressed genes (DEGs) associated to disease severity. One module, correlated with severe cases and older patients, had an overrepresentation of genes involved in innate immune response and in neutrophil activation, whereas two other modules, correlated with disease severity and younger patients, harbored genes involved in the innate immune response to viral infections, and in the regulation of this response. This transcriptomic mechanism could be related to the better outcome observed in younger COVID-19 patients. The DEGs, all hyper-expressed in the group of severe cases, were mostly involved in neutrophil activation and in the p53 pathway, therefore related to inflammation and lymphopenia. These biomarkers may be useful for getting a better stratification of risk factors in COVID-19.

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Section: Resultsmentioning

confidence: 99%

Blood leukocyte transcriptional modules and differentially expressed genes associated with disease severity and age in COVID-19 patients

Bando

Bertonha

Vieira

et al. 2023

Sci Rep

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show abstract

“…The Hhub WASHC5 codes for strumpellin, a protein involved in endosomal fission [46] that was shown to interact directly with SARS-CoV-2 [47]. The Hhub CNOT8 encodes the CNOT8 catalytic subunit of the CCR4-NOT complex, which is required for selective mRNA degradation (mRNA surveillance) and for preventing excessive inflammatory responses [48]. The eHub PSMD10 codes for gankyrin and promotes autophagy [49], a crucial innate immune response against infection.…”

Section: Magenta Modulementioning

confidence: 99%

Blood Leukocyte Transcriptional Modules and Differentially Expressed Genes Associated with Disease Severity and Age in COVID-19 Patients

Bando¹,

Bertonha²,

Vieira³

et al. 2022

Preprint

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The transcriptional response of human blood leukocytes to SARS-CoV-2 infection was investigated focusing on the differences between mild and severe cases and between age subgroups. Weighted gene co-expression network analysis and comparative gene expression analysis were used. Three transcriptional modules positively associated with the traits of interest and their respective high hierarchy genes were identified. Enrichment analyses showed that the yellow module, associated with severe cases and older patients, had an overrepresentation of genes involved in inflammatory and innate immune responses, and neutrophil activation. The magenta and black modules, associated with disease severity and younger patients, contained genes related to innate immunity and inflammation and genes that regulate those responses. Subnetworks for these modules were constructed using genes enriched for innate immunity, inflammation, immunoregulation and differentially expressed genes (severe vs. mild). Their analysis evidenced that immunoregulatory functions are more activated in the modules associated with younger patients, what may help to explain the better disease course and faster recovery observed in younger COVID-19 patients. Comparative gene expression analysis between severe and mild groups, followed by gene enrichment and normalized gene expression analyses, revelated a set of 23 potential biomarkers for COVID-19 severity, of which 13 are newly described.

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“…The second class is the mRNA decay system that actively regulates amounts of mRNA encoding functional proteins. Exonuclease and endonuclease mRNA decay pathways mainly contribute to this "active" mRNA decay (14,16,20). In addition, some recent studies have proposed involvement of the NMD mechanism in regulation of mRNAs encoding full-length proteins during embryonic development and tissue-specific cell differentiation (18,21).…”

Section: Mrna Decay Mechanismsmentioning

confidence: 99%

“…In addition, mRNA decay pathways actively regulate mRNA abundance, which is necessary to maintain and alter mRNA quantity in response to physiological signals. Many studies have suggested that active regulation of mRNA decay mechanisms must be critical for immune regulation and homeostasis (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In this review, we focus on functions of the mRNA decay system regulated by the carbon catabolite repression 4 (CCR4)-negative on TATA-less (NOT) deadenylase complex in early lymphocyte development.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Early Lymphocyte Development via mRNA Decay Catalyzed by the CCR4-NOT Complex

Akiyama

Yamamoto

2021

Front. Immunol.

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Development of lymphocytes is precisely regulated by various mechanisms. In addition to transcriptional rates, post-transcriptional regulation of mRNA abundance contributes to differentiation of lymphocytes. mRNA decay is a post-transcriptional mechanism controlling mRNA abundance. The carbon catabolite repression 4 (CCR4)-negative on TATA-less (NOT) complex controls mRNA longevity by catalyzing mRNA deadenylation, which is the rate-limiting step in the mRNA decay pathway. mRNA decay, regulated by the CCR4-NOT complex, is required for differentiation of pro-B to pre-B cells and V(D)J recombination in pro-B cells. In this process, it is likely that the RNA-binding proteins, ZFP36 ring finger protein like 1 and 2, recruit the CCR4-NOT complex to specific target mRNAs, thereby inducing cell quiescence of pro-B cells. A recent study showed that the CCR4-NOT complex participates in positive selection of thymocytes. Mechanistically, the CCR4-NOT deadenylase complex inhibits abnormal apoptosis by reducing the expression level of mRNAs encoding pro-apoptotic proteins, which are otherwise up-regulated during positive selection. We discuss mechanisms regulating CCR4-NOT complex-dependent mRNA decay in lymphocyte development and selection.

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RNA decay machinery safeguards immune cell development and immunological responses

Cited by 9 publications

References 120 publications

Blood leukocyte transcriptional modules and differentially expressed genes associated with disease severity and age in COVID-19 patients

Blood leukocyte transcriptional modules and differentially expressed genes associated with disease severity and age in COVID-19 patients

Blood Leukocyte Transcriptional Modules and Differentially Expressed Genes Associated with Disease Severity and Age in COVID-19 Patients

Regulation of Early Lymphocyte Development via mRNA Decay Catalyzed by the CCR4-NOT Complex

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