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Pan cancer characterization of genes whose expression has been associated with LINE-1 antisense promoter activity. 表达与LINE-1反义启动子活性相关的基因的泛癌症特征。
IF 4.9 2区 生物学
Mobile DNA Pub Date : 2023-09-18 DOI: 10.1186/s13100-023-00300-x
Baohong Xu, Xueer Li, Shaoqi Zhang, Meina Lian, Wenbin Huang, Yin Zhang, Yudong Wang, Zhiquan Huang
{"title":"Pan cancer characterization of genes whose expression has been associated with LINE-1 antisense promoter activity.","authors":"Baohong Xu,&nbsp;Xueer Li,&nbsp;Shaoqi Zhang,&nbsp;Meina Lian,&nbsp;Wenbin Huang,&nbsp;Yin Zhang,&nbsp;Yudong Wang,&nbsp;Zhiquan Huang","doi":"10.1186/s13100-023-00300-x","DOIUrl":"10.1186/s13100-023-00300-x","url":null,"abstract":"<p><strong>Background: </strong>Long interspersed nuclear element-1 (LINE-1 or L1) comprises 17% of the human genome. As the only autonomous and active retrotransposons, L1 may take part in cancer initiation and progression in some ways. The studies of L1 in cancer mainly focus on the impact of L1 insertion into the new genome locus. The L1 5´ untranslated region (UTR) also contains antisense promoter (ASP) activity, generating L1-gene chimeric transcripts to a neighbor exon. Some of these ASP-associated genes have been reported to be overexpressed in cancer and promote cancer cell growth. However, little is known about overall expression patterns and the roles of L1 ASP-associated genes in human cancers.</p><p><strong>Results: </strong>L1 ASP-associated genes were frequently dysregulated in cancer and associated with the cell cycle, the PI3K/AKT pathway, and the GTPase signaling pathway. The expression of L1 ASP-associated genes was correlated with tumor patient prognosis. Hub L1 ASP-associated genes CENPU and MCM2 showed a correlation with immune infiltration, clinical T stage, and cancer stemness in pan-cancer. Knockdown of L1 ASP-associated gene LINC00491 resulted in a significant decrease in tumor growth and migration ability.</p><p><strong>Conclusions: </strong>The expression of L1 ASP-associated genes is significantly dysregulated at the pan-cancer level, which is closely related to the tumor microenvironment, progression, and patient prognosis. Hub genes CENPU and MCM2 are expected to be new tumor diagnostic markers and therapeutic targets.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"13"},"PeriodicalIF":4.9,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10314111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retro-miRs: novel and functional miRNAs originating from mRNA retrotransposition. 逆转录mirs:源于mRNA逆转录转位的新型功能性mirna。
IF 4.9 2区 生物学
Mobile DNA Pub Date : 2023-09-08 DOI: 10.1186/s13100-023-00301-w
Rafael L V Mercuri, Helena B Conceição, Gabriela D A Guardia, Gabriel Goldstein, Maria D Vibranovski, Ludwig C Hinske, Pedro A F Galante
{"title":"Retro-miRs: novel and functional miRNAs originating from mRNA retrotransposition.","authors":"Rafael L V Mercuri, Helena B Conceição, Gabriela D A Guardia, Gabriel Goldstein, Maria D Vibranovski, Ludwig C Hinske, Pedro A F Galante","doi":"10.1186/s13100-023-00301-w","DOIUrl":"10.1186/s13100-023-00301-w","url":null,"abstract":"<p><strong>Background: </strong>Reverse-transcribed gene copies (retrocopies) have emerged as major sources of evolutionary novelty. MicroRNAs (miRNAs) are small and highly conserved RNA molecules that serve as key post-transcriptional regulators of gene expression. The origin and subsequent evolution of miRNAs have been addressed but not fully elucidated.</p><p><strong>Results: </strong>In this study, we performed a comprehensive investigation of miRNA origination through retroduplicated mRNA sequences (retro-miRs). We identified 17 retro-miRs that emerged from the mRNA retrocopies. Four of these retro-miRs had de novo origins within retrocopied sequences, while 13 retro-miRNAs were located within exon regions and duplicated along with their host mRNAs. We found that retro-miRs were primate-specific, including five retro-miRs conserved among all primates and two human-specific retro-miRs. All retro-miRs were expressed, with predicted and experimentally validated target genes except miR-10527. Notably, the target genes of retro-miRs are involved in key biological processes such as metabolic processes, cell signaling, and regulation of neurotransmitters in the central nervous system. Additionally, we found that these retro-miRs play a potential oncogenic role in cancer by targeting key cancer genes and are overexpressed in several cancer types, including liver hepatocellular carcinoma and stomach adenocarcinoma.</p><p><strong>Conclusions: </strong>Our findings demonstrated that mRNA retrotransposition is a key mechanism for the generation of novel miRNAs (retro-miRs) in primates. These retro-miRs are expressed, conserved, have target genes with important cellular functions, and play important roles in cancer.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"12"},"PeriodicalIF":4.9,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10253462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SARS-CoV-2 infection induces epigenetic changes in the LTR69 subfamily of endogenous retroviruses. SARS-CoV-2感染诱导内源性逆转录病毒LTR69亚家族的表观遗传变化。
IF 4.9 2区 生物学
Mobile DNA Pub Date : 2023-09-04 DOI: 10.1186/s13100-023-00299-1
Ankit Arora, Jan Eric Kolberg, Smitha Srinivasachar Badarinarayan, Natalia Savytska, Daksha Munot, Martin Müller, Veronika Krchlíková, Daniel Sauter, Vikas Bansal
{"title":"SARS-CoV-2 infection induces epigenetic changes in the LTR69 subfamily of endogenous retroviruses.","authors":"Ankit Arora, Jan Eric Kolberg, Smitha Srinivasachar Badarinarayan, Natalia Savytska, Daksha Munot, Martin Müller, Veronika Krchlíková, Daniel Sauter, Vikas Bansal","doi":"10.1186/s13100-023-00299-1","DOIUrl":"10.1186/s13100-023-00299-1","url":null,"abstract":"<p><p>Accumulating evidence suggests that endogenous retroviruses (ERVs) play an important role in the host response to infection and the development of disease. By analyzing ChIP-sequencing data sets, we show that SARS-CoV-2 infection induces H3K27 acetylation of several loci within the LTR69 subfamily of ERVs. Using functional assays, we identified one SARS-CoV-2-activated LTR69 locus, termed Dup69, which exhibits regulatory activity and is responsive to the transcription factors IRF3 and p65/RELA. LTR69_Dup69 is located about 500 bp upstream of a long non-coding RNA gene (ENSG00000289418) and within the PTPRN2 gene encoding a diabetes-associated autoantigen. Both ENSG00000289418 and PTPRN2 showed a significant increase in expression upon SARS-CoV-2 infection. Thus, our study sheds light on the interplay of exogenous with endogenous viruses and helps to understand how ERVs regulate gene expression during infection.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"11"},"PeriodicalIF":4.9,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Themes and variations on piRNA-guided transposon control. pirna引导转座子控制的主题和变化。
IF 4.9 2区 生物学
Mobile DNA Pub Date : 2023-09-02 DOI: 10.1186/s13100-023-00298-2
Zuzana Loubalova, Parthena Konstantinidou, Astrid D Haase
{"title":"Themes and variations on piRNA-guided transposon control.","authors":"Zuzana Loubalova, Parthena Konstantinidou, Astrid D Haase","doi":"10.1186/s13100-023-00298-2","DOIUrl":"10.1186/s13100-023-00298-2","url":null,"abstract":"<p><p>PIWI-interacting RNAs (piRNAs) are responsible for preventing the movement of transposable elements in germ cells and protect the integrity of germline genomes. In this review, we examine the common elements of piRNA-guided silencing as well as the differences observed between species. We have categorized the mechanisms of piRNA biogenesis and function into modules. Individual PIWI proteins combine these modules in various ways to produce unique PIWI-piRNA pathways, which nevertheless possess the ability to perform conserved functions. This modular model incorporates conserved core mechanisms and accommodates variable co-factors. Adaptability is a hallmark of this RNA-based immune system. We believe that considering the differences in germ cell biology and resident transposons in different organisms is essential for placing the variations observed in piRNA biology into context, while still highlighting the conserved themes that underpin this process.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"10"},"PeriodicalIF":4.9,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10474768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10170691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transposable elements as essential elements in the control of gene expression. 转座因子是调控基因表达的重要因子。
IF 4.7 2区 生物学
Mobile DNA Pub Date : 2023-08-18 DOI: 10.1186/s13100-023-00297-3
Alemu Gebrie
{"title":"Transposable elements as essential elements in the control of gene expression.","authors":"Alemu Gebrie","doi":"10.1186/s13100-023-00297-3","DOIUrl":"10.1186/s13100-023-00297-3","url":null,"abstract":"<p><p>Interspersed repetitions called transposable elements (TEs), commonly referred to as mobile elements, make up a significant portion of the genomes of higher animals. TEs contribute in controlling the expression of genes locally and even far away at the transcriptional and post-transcriptional levels, which is one of their significant functional effects on gene function and genome evolution. There are different mechanisms through which TEs control the expression of genes. First, TEs offer cis-regulatory regions in the genome with their inherent regulatory features for their own expression, making them potential factors for controlling the expression of the host genes. Promoter and enhancer elements contain cis-regulatory sites generated from TE, which function as binding sites for a variety of trans-acting factors. Second, a significant portion of miRNAs and long non-coding RNAs (lncRNAs) have been shown to have TEs that encode for regulatory RNAs, revealing the TE origin of these RNAs. Furthermore, it was shown that TE sequences are essential for these RNAs' regulatory actions, which include binding to the target mRNA. By being a member of cis-regulatory and regulatory RNA sequences, TEs therefore play essential regulatory roles. Additionally, it has been suggested that TE-derived regulatory RNAs and cis-regulatory regions both contribute to the evolutionary novelty of gene regulation. Additionally, these regulatory systems arising from TE frequently have tissue-specific functions. The objective of this review is to discuss TE-mediated gene regulation, with a particular emphasis on the processes, contributions of various TE types, differential roles of various tissue types, based mostly on recent studies on humans.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"9"},"PeriodicalIF":4.7,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reproducible evaluation of transposable element detectors with McClintock 2 guides accurate inference of Ty insertion patterns in yeast. 用McClintock 2对转座元件检测器的可重复性评价指导了酵母中Ty插入模式的准确推断。
IF 4.9 2区 生物学
Mobile DNA Pub Date : 2023-07-14 DOI: 10.1186/s13100-023-00296-4
Jingxuan Chen, Preston J Basting, Shunhua Han, David J Garfinkel, Casey M Bergman
{"title":"Reproducible evaluation of transposable element detectors with McClintock 2 guides accurate inference of Ty insertion patterns in yeast.","authors":"Jingxuan Chen,&nbsp;Preston J Basting,&nbsp;Shunhua Han,&nbsp;David J Garfinkel,&nbsp;Casey M Bergman","doi":"10.1186/s13100-023-00296-4","DOIUrl":"https://doi.org/10.1186/s13100-023-00296-4","url":null,"abstract":"<p><strong>Background: </strong>Many computational methods have been developed to detect non-reference transposable element (TE) insertions using short-read whole genome sequencing data. The diversity and complexity of such methods often present challenges to new users seeking to reproducibly install, execute, or evaluate multiple TE insertion detectors.</p><p><strong>Results: </strong>We previously developed the McClintock meta-pipeline to facilitate the installation, execution, and evaluation of six first-generation short-read TE detectors. Here, we report a completely re-implemented version of McClintock written in Python using Snakemake and Conda that improves its installation, error handling, speed, stability, and extensibility. McClintock 2 now includes 12 short-read TE detectors, auxiliary pre-processing and analysis modules, interactive HTML reports, and a simulation framework to reproducibly evaluate the accuracy of component TE detectors. When applied to the model microbial eukaryote Saccharomyces cerevisiae, we find substantial variation in the ability of McClintock 2 components to identify the precise locations of non-reference TE insertions, with RelocaTE2 showing the highest recall and precision in simulated data. We find that RelocaTE2, TEMP, TEMP2 and TEBreak provide consistent estimates of [Formula: see text]50 non-reference TE insertions per strain and that Ty2 has the highest number of non-reference TE insertions in a species-wide panel of [Formula: see text]1000 yeast genomes. Finally, we show that best-in-class predictors for yeast applied to resequencing data have sufficient resolution to reveal a dyad pattern of integration in nucleosome-bound regions upstream of yeast tRNA genes for Ty1, Ty2, and Ty4, allowing us to extend knowledge about fine-scale target preferences revealed previously for experimentally-induced Ty1 insertions to spontaneous insertions for other copia-superfamily retrotransposons in yeast.</p><p><strong>Conclusion: </strong>McClintock ( https://github.com/bergmanlab/mcclintock/ ) provides a user-friendly pipeline for the identification of TEs in short-read WGS data using multiple TE detectors, which should benefit researchers studying TE insertion variation in a wide range of different organisms. Application of the improved McClintock system to simulated and empirical yeast genome data reveals best-in-class methods and novel biological insights for one of the most widely-studied model eukaryotes and provides a paradigm for evaluating and selecting non-reference TE detectors in other species.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"8"},"PeriodicalIF":4.9,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10347736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9863184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Host range of strand-biased circularizing integrative elements: a new class of mobile DNA elements nesting in Gammaproteobacteria. 偏链循环整合元件的宿主范围:一类新的移动DNA元件在γ变形菌中嵌套。
IF 4.9 2区 生物学
Mobile DNA Pub Date : 2023-05-26 DOI: 10.1186/s13100-023-00295-5
Desmila Idola, Hiroshi Mori, Yuji Nagata, Lisa Nonaka, Hirokazu Yano
{"title":"Host range of strand-biased circularizing integrative elements: a new class of mobile DNA elements nesting in Gammaproteobacteria.","authors":"Desmila Idola,&nbsp;Hiroshi Mori,&nbsp;Yuji Nagata,&nbsp;Lisa Nonaka,&nbsp;Hirokazu Yano","doi":"10.1186/s13100-023-00295-5","DOIUrl":"https://doi.org/10.1186/s13100-023-00295-5","url":null,"abstract":"<p><strong>Background: </strong>The strand-biased circularizing integrative elements (SEs) are putatively non-mobilizable integrative elements for transmitting antimicrobial resistance genes. The transposition mode and the prevalence of SEs in prokaryotes remain vague.</p><p><strong>Results: </strong>To corroborate the transposition mode and the prevalence of SEs, hypothetical transposition intermediates of an SE were searched for in genomic DNA fractions of an SE host. Then, the SE core genes were defined based on gene knockout experiments, and the synteny blocks of their distant homologs were searched for in the RefSeq complete genome sequence database using PSI-BLAST. A genomic DNA fractionation experiment revealed that SE copies are present in a double-stranded nicked circular form in vivo. Operonic structure of three conserved coding sequences (intA, tfp, intB) and srap located at the left end of SEs were identified as essential for attL × attR recombination. The synteny blocks of tfp and srap homologs were detected in 3.6% of the replicons of Gammaproteobacteria but not in other taxa, implying that SE movement is host-dependent. SEs have been discovered most frequently in the orders Vibrionales (19% of replicons), Pseudomonadales (18%), Alteromonadales (17%), and Aeromonadales (12%). Genomic comparisons revealed 35 new SE members with identifiable termini. SEs are present at 1 to 2 copies per replicon and have a median length of 15.7 kb. Three newly identified SE members carry antimicrobial resistance genes, like tmexCD-toprJ, mcr-9, and bla<sub>GMA-1</sub>. Further experiments validated that three new SE members possess the strand-biased attL × attR recombination activity.</p><p><strong>Conclusions: </strong>This study suggested that transposition intermediates of SEs are double-stranded circular DNA. The main hosts of SEs are a subset of free-living Gammaproteobacteria; this represents a rather narrow host range compared to those of mobile DNA element groups discovered to date. As the host range, genetic organization, and movements are unique among the mobile DNA elements, SEs provide a new model system for host-mobile DNA element coevolution studies.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"7"},"PeriodicalIF":4.9,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9532139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
THE1B may have no role in human pregnancy due to ZNF430-mediated silencing. 由于znf430介导的沉默,THE1B可能在人类妊娠中没有作用。
IF 4.9 2区 生物学
Mobile DNA Pub Date : 2023-05-22 DOI: 10.1186/s13100-023-00294-6
Zheng Zuo
{"title":"THE1B may have no role in human pregnancy due to ZNF430-mediated silencing.","authors":"Zheng Zuo","doi":"10.1186/s13100-023-00294-6","DOIUrl":"https://doi.org/10.1186/s13100-023-00294-6","url":null,"abstract":"<p><p>THE1-family retrovirus invaded the primate genome more than 40 million years ago. Dunn-Fletcher et al. reported one THE1B element upstream of CRH gene alters gestation length by upregulating corticotropin-releasing hormone expression in transgenic mice and concluded it has the same role in human as well. However, no promoter or enhancer mark has been detected around this CRH-proximal element in any human tissue or cell, so probably some anti-viral factor exists in primates to prevents it from wreaking havoc. Here I report two paralogous zinc finger genes, ZNF430 and ZNF100, that emerged during the simian lineage to specifically silence THE1B and THE1A, respectively. Contact residue changes in one finger confers each ZNF the unique ability to preferentially repress one THE1 sub-family over the other. The reported THE1B element contains an intact ZNF430 binding site, thus under the repression of ZNF430 in most tissues including placenta, it is questionable whether or not this retrovirus has any role in human pregnancy. Overall, this analysis highlights the need to study human retroviruses' functions in suitable model system.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"6"},"PeriodicalIF":4.9,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9508945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Expression of L1 retrotransposons in granulocytes from patients with active systemic lupus erythematosus. 活动性系统性红斑狼疮患者粒细胞中L1反转录转座子的表达。
IF 4.9 2区 生物学
Mobile DNA Pub Date : 2023-05-10 DOI: 10.1186/s13100-023-00293-7
Kennedy C Ukadike, Rayan Najjar, Kathryn Ni, Amanda Laine, Xiaoxing Wang, Alison Bays, Martin S Taylor, John LaCava, Tomas Mustelin
{"title":"Expression of L1 retrotransposons in granulocytes from patients with active systemic lupus erythematosus.","authors":"Kennedy C Ukadike, Rayan Najjar, Kathryn Ni, Amanda Laine, Xiaoxing Wang, Alison Bays, Martin S Taylor, John LaCava, Tomas Mustelin","doi":"10.1186/s13100-023-00293-7","DOIUrl":"10.1186/s13100-023-00293-7","url":null,"abstract":"<p><strong>Background: </strong>Patients with systemic lupus erythematosus (SLE) have autoantibodies against the L1-encoded open-reading frame 1 protein (ORF1p). Here, we report (i) which immune cells ORF1p emanates from, (ii) which L1 loci are transcriptionally active, (iii) whether the cells express L1-dependent interferon and interferon-stimulated genes, and (iv) the effect of inhibition of L1 ORF2p by reverse transcriptase inhibitors.</p><p><strong>Results: </strong>L1 ORF1p was detected by flow cytometry primarily in SLE CD66b<sup>+</sup>CD15<sup>+</sup> regular and low-density granulocytes, but much less in other immune cell lineages. The amount of ORF1p was higher in neutrophils from patients with SLE disease activity index (SLEDAI) > 6 (p = 0.011) compared to patients with inactive disease, SLEDAI < 4. Patient neutrophils transcribed seven to twelve human-specific L1 loci (L1Hs), but only 3 that are full-length and with an intact ORF1. Besides serving as a source of detectable ORF1p, the most abundant transcript encoded a truncated ORF2p reverse transcriptase predicted to remain cytosolic, while the two other encoded an intact full-length ORF2p. A number of genes encoding proteins that influence L1 transcription positively or negatively were altered in patients, particularly those with active disease, compared to healthy controls. Components of nucleic acid sensing and interferon induction were also altered. SLE neutrophils also expressed type I interferon-inducible genes and interferon β, which were substantially reduced after treatment of the cells with drugs known to inhibit ORF2p reverse transcriptase activity.</p><p><strong>Conclusions: </strong>We identified L1Hs loci that are transcriptionally active in SLE neutrophils, and a reduction in the epigenetic silencing mechanisms that normally counteract L1 transcription. SLE neutrophils contained L1-encoded ORF1p protein, as well as activation of the type I interferon system, which was inhibited by treatment with reverse transcriptase inhibitors. Our findings will enable a deeper analysis of L1 dysregulation and its potential role in SLE pathogenesis.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"5"},"PeriodicalIF":4.9,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10439218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of antibiotic resistance gene cassettes in a newly identified Salmonella enterica serovar Gallinarum strain in Korea. 韩国一株新发现的鸡血清型肠炎沙门氏菌耐药基因磁带分析。
IF 4.9 2区 生物学
Mobile DNA Pub Date : 2023-04-24 DOI: 10.1186/s13100-023-00292-8
Thanh Quang Tran, Minyoung Park, Jong Eun Lee, Soo Hyun Kim, Jae-Ho Jeong, Hyon E Choy
{"title":"Analysis of antibiotic resistance gene cassettes in a newly identified Salmonella enterica serovar Gallinarum strain in Korea.","authors":"Thanh Quang Tran,&nbsp;Minyoung Park,&nbsp;Jong Eun Lee,&nbsp;Soo Hyun Kim,&nbsp;Jae-Ho Jeong,&nbsp;Hyon E Choy","doi":"10.1186/s13100-023-00292-8","DOIUrl":"https://doi.org/10.1186/s13100-023-00292-8","url":null,"abstract":"<p><p>Antimicrobial resistant pathogens are a global health threat driven by the indiscriminate use of antimicrobials. Antimicrobial resistance can be acquired by resistance genes encoded by mobile genetic elements. In this study, we identified a strain of Salmonella enterica serovar Gallinarum (SG4021) from an infected chicken in Korea and characterized the presence of resistance genes in its plasmid by whole genome sequencing. The sequence was then compared with that of a plasmid (P2) from strain SG_07Q015, the only other strain of S. Gallinarum isolated in Korea for which a genome sequence is available. The results revealed that both strains harbored nearly identical DNA carrying antibiotic resistance gene cassettes inserted into integron In2 of the transposable element Tn21, namely an aadA1 resistance gene conferring resistance to aminoglycosides and a sul1 resistance gene conferring resistance to sulfonamide. Interestingly, despite the presence of sul1 in SG4021, an antibiotic sensitivity test revealed that it was sensitive to sulfonamides. Further analysis revealed that this disparity was due to the insertion of a ~ 5 kb ISCR16 sequence downstream of the promoter driving sul1 expression in SG4021. Using various mutants, we showed that the insertion of ISCR16 blocked the expression of the sul1 gene from the upstream promoter. Therefore, the functionality of antimicrobial resistance genes determines phenotypic antimicrobial resistance.</p>","PeriodicalId":18854,"journal":{"name":"Mobile DNA","volume":"14 1","pages":"4"},"PeriodicalIF":4.9,"publicationDate":"2023-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10124037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9391068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
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