The Molecular Evolution and Functional Divergence of Lamprey Programmed Cell Death Genes

Guan, Xin; Lü, Jian; Sun, Feng; Li, Qingwei; Pang, Yue

doi:10.3389/fimmu.2019.01382

Cited by 27 publications

(29 citation statements)

References 64 publications

(58 reference statements)

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“… 36 Both apoptosis and cell proliferation are precisely regulated by genes to ensure the dynamic balance of the number of cells in the body. 37 It has been found that the damage to articular cartilage and bone tissue in the process of RA is closely related to the excessive proliferation of synovial cells and insufficient apoptosis. 38 , 39 …”

Section: Discussionmentioning

confidence: 99%

Transcriptome-Wide High-Throughput m6A Sequencing of Differential m6A Methylation Patterns in the Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes Cell Line MH7A

Jiang

Cao²,

Chang

et al. 2021

JIR

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Introduction N6-methyladenosine (m6A) is the most frequent internal modification in eukaryotic mRNAs and is closely related to the occurrence and development of many diseases, especially tumors. However, the relationship between m6A methylation and rheumatoid arthritis (RA) is still a mystery. Methods Two high-throughput sequencing methods, namely, m6A modified RNA immunoprecipitation sequence (m6A-seq) and RNA sequence (RNA-seq) were performed to identify the differentially expressed m6A methylation in human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A after stimulation with TNF-α. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to obtain enriched GO terms and significant KEGG pathways. Then, four candidate genes, Wilms tumor 1-associating protein (WTAP), receptor-interacting serine/threonine protein kinase 2 (RIPK2), Janus kinase 3 (JAK3) and tumor necrosis factor receptor SF10A (TNFRSF10A) were selected to further validate the m6A methylation, mRNA and protein expression levels in MH7A cells and synovial tissues of adjuvant arthritis (AA) rats by RT-qPCR and Western blot. Results Using m6A-seq, we identified a total of 206 genes with differentially expressed m6A methylation, of which 118 were significantly upregulated and 88 genes were significantly downregulated. Likewise, 1207 differentially mRNA expressed mRNAs were obtained by RNA-seq, of which 793 were upregulated and 414 downregulated. Further joint analysis showed that the m6A methylation and mRNA expression levels of 88 genes changed significantly, of which 30 genes displayed increased m6A methylation and decreased mRNA expression, 57 genes displayed decreased m6A methylation and increased mRNA expression increased, and 1 gene displayed increased m6A methylation and increased mRNA expression. GO and KEGG analyses indicated that these unique genes were mainly enriched in inflammation-related pathways, cell proliferation and apoptosis. In addition, the validations of WTAP, RIPK2, JAK3 and TNFRSF10A were in accordance with the m6A and RNA sequencing results. Conclusion This study established the transcriptional map of m6A in MH7A cells and revealed the potential relationship between RNA methylation modification and RA related genes. The results suggested that m6A modification was associated with the occurrence and course of RA to some extent.

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Section: Discussionmentioning

confidence: 99%

Transcriptome-Wide High-Throughput m6A Sequencing of Differential m6A Methylation Patterns in the Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes Cell Line MH7A

Jiang

Cao²,

Chang

et al. 2021

JIR

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“…The PBS group was used as a control group. Then, leukocyte RNA was extracted and reversetranscribed with a PrimeScript RT-PCR kit (TaKaRa, China) (34). Importantly, the genomic DNA was removed according to the instructions to eliminate interference.…”

Section: Quantitative Rt-pcrmentioning

confidence: 99%

“…qPCR was performed in triplicate using a TaKaRa PCR Thermal Cycler Dice Real Time System, and L-gapdh (GenBank accession No. KU041137.1) was used as an internal control (28,29,34). The reaction efficiency was tested by the gradual dilution of cDNA template (1x, 5x, 10x, 20x, and 40x).…”

Section: Quantitative Rt-pcrmentioning

confidence: 99%

Comprehensive Evolutionary Analysis of Lamprey TNFR-Associated Factors (TRAFs) and Receptor-Interacting Protein Kinase (RIPKs) and Insights Into the Functional Characterization of TRAF3/6 and RIPK1

Hou

Pang

2020

Front. Immunol.

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TNFR-associated factors (TRAFs) and receptor-interacting protein kinases (RIPKs) are important immunological linker molecules in mammals and play important roles in the TNFα, TLR and IFN signaling pathways. However, the evolutionary origins of these genes in vertebrates have not previously been described in lampreys. In this study, we searched the genomes of Lampetra japonicum, Lethenteron reissneri, and Petromyzon marinus for genes encoding trafs and ripks and performed homologous sequence alignment, phylogenetic tree, functional domain, conserved motif, gene structure, and synteny analyses to determine their evolutionary relationships. The distribution of the lamprey traf and ripk families and the immune response of the gene families in lampreys stimulated by different pathogens were also demonstrated, suggesting a role of structural changes in expression and functional diversification. Additionally, the dual luciferase reporter gene assay showed that the addition of exogenous immunomodulator (TNFα or IFN) to the overexpression of LjLRIPK1a or LjTRAF3/6 significantly downregulated NF-κB or ISRE activation. LjRIPK1a can significantly enhance caspase-8 activity, and overexpression of LjRIPK1a or LjTRAF3a/6 in HEK293T cells results in cell apoptosis. In summary, this study makes an important contribution to the understanding of the traf and ripk gene families in different vertebrates. Our results also provide new evidence for the evolution of vertebrate TRAFs and RIPKs and their impacts on immune regulation.

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“…The transition from jawless to jawed vertebrates was caused by some significant evolutionary events, including gene origination and evolution, gene duplication, and cell population and tissue structure changes. Due to its unique evolutionary status, lampreys are essential for exploring the evolution of vertebrates and the origin of different functional mechanisms ( Smith et al, 2018 ; Guan et al, 2019 ). In addition, lampreys are typical migratory organisms that live in the ocean for part of the year.…”

Section: Introductionmentioning

confidence: 99%

Genetic and Functional Characterization of Novel Brown-Like Adipocytes Around the Lamprey Brain

et al. 2021

Front. Cell Dev. Biol.

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During the process of vertebrate evolution, many thermogenic organs and mechanisms have appeared. Mammalian brown adipose tissue (BAT) generates heat through the uncoupling oxidative phosphorylation of mitochondria, acts as a natural defense against hypothermia and inhibits the development of obesity. Although the existence, cellular origin and molecular identity of BAT in humans have been well studied, the genetic and functional characteristics of BAT from lampreys remain unknown. Here, we identified and characterized a novel, naturally existing brown-like adipocytes at the lamprey brain periphery. Similar to human BAT, the lamprey brain periphery contains brown-like adipocytes that maintain the same morphology as human brown adipocytes, containing multilocular lipid droplets and high mitochondrion numbers. Furthermore, we found that brown-like adipocytes in the periphery of lamprey brains responded to thermogenic reagent treatment and cold exposure and that lamprey UCP2 promoted precursor adipocyte differentiation. Molecular mapping by RNA-sequencing showed that inflammation in brown-like adipocytes treated with LPS and 25HC was enhanced compared to controls. The results of this study provide new evidence for human BAT research and demonstrate the multilocular adipose cell functions of lampreys, including: (1) providing material energy and protecting structure, (2) generating additional heat and contributing to adaptation to low-temperature environments, and (3) resisting external pathogens.

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The Molecular Evolution and Functional Divergence of Lamprey Programmed Cell Death Genes

Cited by 27 publications

References 64 publications

Transcriptome-Wide High-Throughput m6A Sequencing of Differential m6A Methylation Patterns in the Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes Cell Line MH7A

Transcriptome-Wide High-Throughput m6A Sequencing of Differential m6A Methylation Patterns in the Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes Cell Line MH7A

Comprehensive Evolutionary Analysis of Lamprey TNFR-Associated Factors (TRAFs) and Receptor-Interacting Protein Kinase (RIPKs) and Insights Into the Functional Characterization of TRAF3/6 and RIPK1

Genetic and Functional Characterization of Novel Brown-Like Adipocytes Around the Lamprey Brain

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