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Proceedings of the inaugural Dark Genome Symposium: November 2022. 首届黑暗基因组研讨会论文集:2022年11月。
IF 4.7 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2023-11-21 DOI: 10.1186/s13100-023-00306-5
Jef D Boeke, Kathleen H Burns, Katherine B Chiappinelli, Marie Classon, John M Coffin, Daniel D DeCarvalho, Joseph D Dukes, Benjamin Greenbaum, George Kassiotis, Sarah K Knutson, Arnold J Levine, Avindra Nath, Sophie Papa, Daniel Rios, John Sedivy, David T Ting

In November 2022 the first Dark Genome Symposium was held in Boston, USA. The meeting was hosted by Rome Therapeutics and Enara Bio, two biotechnology companies working on translating our growing understanding of this vast genetic landscape into therapies for human disease. The spirit and ambition of the meeting was one of shared knowledge, looking to strengthen the network of researchers engaged in the field. The meeting opened with a welcome from Rosana Kapeller and Kevin Pojasek followed by a first session of field defining talks from key academics in the space. A series of panels, bringing together academia and industry views, were then convened covering a wide range of pertinent topics. Finally, Richard Young and David Ting gave their views on the future direction and promise for patient impact inherent in the growing understanding of the Dark Genome.

2022年11月,首届黑暗基因组研讨会在美国波士顿举行。会议由Rome Therapeutics和Enara Bio主办,这两家生物技术公司致力于将我们对这一巨大遗传景观的日益增长的理解转化为人类疾病的治疗方法。会议的精神和目标是分享知识,希望加强从事该领域的研究人员的网络。会议以Rosana Kapeller和Kevin Pojasek的欢迎词开场,随后是该领域主要学者的第一届领域界定演讲。随后召开了一系列小组会议,汇集了学术界和工业界的观点,涵盖了广泛的相关主题。最后,Richard Young和David Ting给出了他们对未来方向的看法,以及对黑暗基因组日益增长的理解所固有的患者影响的承诺。
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引用次数: 0
Long noncoding RNAs emerge from transposon-derived antisense sequences and may contribute to infection stage-specific transposon regulation in a fungal phytopathogen. 长非编码rna来自转座子衍生的反义序列,可能有助于真菌植物病原体感染阶段特异性转座子调控。
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2023-11-15 DOI: 10.1186/s13100-023-00305-6
Jiangzhao Qian, Heba M M Ibrahim, Myriam Erz, Florian Kümmel, Ralph Panstruga, Stefan Kusch

Background: The genome of the obligate biotrophic phytopathogenic barley powdery mildew fungus Blumeria hordei is inflated due to highly abundant and possibly active transposable elements (TEs). In the absence of the otherwise common repeat-induced point mutation transposon defense mechanism, noncoding RNAs could be key for regulating the activity of TEs and coding genes during the pathogenic life cycle.

Results: We performed time-course whole-transcriptome shotgun sequencing (RNA-seq) of total RNA derived from infected barley leaf epidermis at various stages of fungal pathogenesis and observed significant transcript accumulation and time point-dependent regulation of TEs in B. hordei. Using a manually curated consensus database of 344 TEs, we discovered phased small RNAs mapping to 104 consensus transposons, suggesting that RNA interference contributes significantly to their regulation. Further, we identified 5,127 long noncoding RNAs (lncRNAs) genome-wide in B. hordei, of which 823 originated from the antisense strand of a TE. Co-expression network analysis of lncRNAs, TEs, and coding genes throughout the asexual life cycle of B. hordei points at extensive positive and negative co-regulation of lncRNAs, subsets of TEs and coding genes.

Conclusions: Our work suggests that similar to mammals and plants, fungal lncRNAs support the dynamic modulation of transcript levels, including TEs, during pivotal stages of host infection. The lncRNAs may support transcriptional diversity and plasticity amid loss of coding genes in powdery mildew fungi and may give rise to novel regulatory elements and virulence peptides, thus representing key drivers of rapid evolutionary adaptation to promote pathogenicity and overcome host defense.

背景:专性生物营养性植物致病性大麦白粉病真菌Blumeria hordei的基因组由于高度丰富且可能活跃的转座因子(te)而膨胀。在缺乏其他常见的重复诱导点突变转座子防御机制的情况下,非编码rna可能是在致病性生命周期中调节TEs和编码基因活性的关键。结果:我们对真菌发病各阶段感染大麦叶表皮的总RNA进行了全转录组鸟枪测序(RNA-seq),观察到显著的转录积累和时间点依赖性的te调控。利用人工整理的344个te的共识数据库,我们发现了定位于104个共识转座子的阶段性小RNA,这表明RNA干扰对它们的调控起着重要作用。此外,我们鉴定出了5127个长链非编码rna (lncRNAs),其中823个来自TE的反义链。对白背蜂无性生命周期中lncRNAs、TEs和编码基因的共表达网络分析表明,lncRNAs、TEs亚群和编码基因存在广泛的正、负共调控。结论:我们的研究表明,与哺乳动物和植物类似,真菌lncRNAs在宿主感染的关键阶段支持转录物水平的动态调节,包括TEs。在白粉病真菌编码基因缺失的情况下,lncrna可能支持转录多样性和可塑性,并可能产生新的调控元件和毒力肽,因此代表了快速进化适应以促进致病性和克服宿主防御的关键驱动因素。
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引用次数: 0
Co-expression of distinct L1 retrotransposon coiled coils can lead to their entanglement. 不同L1反转录转座子盘绕线圈的共同表达可以导致它们的纠缠。
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2023-10-20 DOI: 10.1186/s13100-023-00303-8
Nikola A Mizgier, Charlie E Jones, Anthony V Furano

L1 (LINE1) non-LTR retrotransposons are ubiquitous genomic parasites and the dominant transposable element in humans having generated about 40% of their genomic DNA during their ~ 100 million years (Myr) of activity in primates. L1 replicates in germ line cells and early embryos, causing genetic diversity and defects, but can be active in some somatic stem cells, tumors and during aging. L1 encodes two proteins essential for retrotransposition: ORF2p, a reverse transcriptase that contains an endonuclease domain, and ORF1p, a coiled coil mediated homo trimer, which functions as a nucleic acid chaperone. Both proteins contain highly conserved domains and preferentially bind their encoding transcript to form an L1 ribonucleoprotein (RNP), which mediates retrotransposition. However, the coiled coil has periodically undergone episodes of substantial amino acid replacement to the extent that a given L1 family can concurrently express multiple ORF1s that differ in the sequence of their coiled coils. Here we show that such distinct ORF1p sequences can become entangled forming heterotrimers when co-expressed from separate vectors and speculate on how coiled coil entanglement could affect coiled coil evolution.

L1(LINE1)非LTR逆转录转座子是普遍存在的基因组寄生虫,是人类中的主要转座子~ 灵长类动物1亿年的活动。L1在生殖系细胞和早期胚胎中复制,导致遗传多样性和缺陷,但在一些体细胞干细胞、肿瘤和衰老过程中可能具有活性。L1编码两种逆转录转座所必需的蛋白质:ORF2p,一种含有核酸内切酶结构域的逆转录酶,和ORF1p,一个卷曲的螺旋介导的同源三聚体,起核酸伴侣的作用。这两种蛋白质都含有高度保守的结构域,并优先结合其编码转录物形成L1核糖核蛋白(RNP),该蛋白介导逆转录转座。然而,盘绕的螺旋体周期性地经历了大量氨基酸置换,以至于给定的L1家族可以同时表达其盘绕的序列不同的多个ORF1。在这里,我们表明,当从单独的载体中共同表达时,这种不同的ORF1p序列可以成为纠缠形成的异源三聚体,并推测卷曲线圈纠缠如何影响卷曲线圈的进化。
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引用次数: 0
Plants acquired mitochondrial linear plasmids horizontally from fungi likely during the conquest of land. 植物可能在征服土地的过程中从真菌那里水平获得线粒体线性质粒。
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2023-10-17 DOI: 10.1186/s13100-023-00304-7
Yutong Wei, Zhen Gong, Guan-Zhu Han

Mitochondrial linear plasmids have been sporadically reported in fungi and plants. Yet, much remains obscure about the diversity, distribution, and evolution of mitochondrial linear plasmids. Here, through phylogenomic analyses across 7,163 cellular organisms (including 991 plants), we find that mitochondrial linear plasmids are widely present in land plants and fungi. Phylogenetic analyses indicate that plants are likely to have acquired mitochondrial linear plasmids horizontally from fungi before or during the conquest of terrestrial environments by plants. Gene content analyses show that mitochondrial linear plasmids harbor a highly dynamic and promiscuous repertoire of genes. Our study refines the understanding of the origin and evolution of mitochondrial linear plasmids.

线粒体线性质粒在真菌和植物中也有零星报道。然而,线粒体线性质粒的多样性、分布和进化仍有很多未知之处。在这里,通过对7163种细胞生物(包括991种植物)的系统发育分析,我们发现线粒体线性质粒广泛存在于陆地植物和真菌中。系统发育分析表明,植物很可能在植物征服陆地环境之前或期间从真菌水平获得线粒体线性质粒。基因含量分析表明,线粒体线性质粒含有高度动态和混杂的基因库。我们的研究完善了对线粒体线性质粒起源和进化的理解。
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引用次数: 0
Teleost genomic repeat landscapes in light of diversification rates and ecology. 根据多样化率和生态学,远隔基因组重复景观。
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2023-10-03 DOI: 10.1186/s13100-023-00302-9
William B Reinar, Ole K Tørresen, Alexander J Nederbragt, Michael Matschiner, Sissel Jentoft, Kjetill S Jakobsen

Repetitive DNA make up a considerable fraction of most eukaryotic genomes. In fish, transposable element (TE) activity has coincided with rapid species diversification. Here, we annotated the repetitive content in 100 genome assemblies, covering the major branches of the diverse lineage of teleost fish. We investigated if TE content correlates with family level net diversification rates and found support for a weak negative correlation. Further, we demonstrated that TE proportion correlates with genome size, but not to the proportion of short tandem repeats (STRs), which implies independent evolutionary paths. Marine and freshwater fish had large differences in STR content, with the most extreme propagation detected in the genomes of codfish species and Atlantic herring. Such a high density of STRs is likely to increase the mutational load, which we propose could be counterbalanced by high fecundity as seen in codfishes and herring.

重复DNA在大多数真核生物基因组中占相当大的比例。在鱼类中,转座元件(TE)的活性与物种的快速多样化相吻合。在这里,我们注释了100个基因组组装中的重复内容,涵盖了硬骨鱼不同谱系的主要分支。我们调查了TE含量是否与家庭层面的净多样化率相关,并发现支持弱负相关。此外,我们证明TE比例与基因组大小相关,但与短串联重复序列(STR)的比例无关,这意味着独立的进化路径。海洋鱼类和淡水鱼类的STR含量差异很大,鳕鱼和大西洋鲱鱼的基因组中检测到最极端的繁殖。如此高密度的STR可能会增加突变负荷,我们认为这可能会被鳕鱼和鲱鱼的高繁殖力所抵消。
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引用次数: 0
Parallel Pairwise Operations on Data Stored in DNA: Sorting, Shifting, and Searching 存储在DNA中的数据的并行成对操作:排序、移动和搜索
IF 4.9 2区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2023-09-21 DOI: 10.4230/LIPIcs.DNA.27.11
Tonglin Chen, Arnav Solanki, Marc D. Riedel
Prior research has introduced the Single-Instruction-Multiple-Data paradigm for DNA computing (SIMD DNA). It offers the potential for storing information and performing in-memory computations on DNA, with massive parallelism. This paper introduces three new SIMD DNA operations: sorting, shifting, and searching. Each is a fundamental operation in computer science. Our implementations demonstrate the effectiveness of parallel pairwise operations with this new paradigm.
先前的研究已经引入了DNA计算的单指令多数据范式(SIMD DNA)。它提供了在DNA上存储信息和执行内存计算的潜力,具有巨大的并行性。本文介绍了三种新的SIMD DNA操作:排序、移动和搜索。每一个都是计算机科学的基本操作。我们的实现演示了使用这种新范式的并行成对操作的有效性。
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引用次数: 4
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 Q1 GENETICS & HEREDITY 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

Background: 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.

Results: 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.

Conclusions: 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.

背景:长散布核元件-1(LINE-1或L1)占人类基因组的17%。L1作为唯一自主和活性的反转录转座子,可能以某些方式参与癌症的发生和发展。L1在癌症中的研究主要集中在L1插入新基因组基因座的影响上。L1 5´非翻译区(UTR)也含有反义启动子(ASP)活性,产生与相邻外显子的L1基因嵌合转录物。据报道,这些ASP相关基因中的一些在癌症中过表达,并促进癌症细胞生长。然而,人们对L1-ASP相关基因在人类癌症中的总体表达模式和作用知之甚少。结果:L1-ASP相关基因在癌症中经常失调,并与细胞周期、PI3K/AKT通路和GTPase信号通路有关。L1 ASP相关基因的表达与肿瘤患者的预后相关。Hub L1 ASP相关基因CENPU和MCM2与全癌患者的免疫浸润、临床T分期和癌症干性相关。L1 ASP相关基因LINC00491的敲除导致肿瘤生长和迁移能力的显著降低。结论:L1 ASP相关基因的表达在全癌水平上显著失调,这与肿瘤微环境、进展和患者预后密切相关。中枢基因CENPU和MCM2有望成为新的肿瘤诊断标志物和治疗靶点。
{"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 Q1 GENETICS & HEREDITY 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

Background: 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.

Results: 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.

Conclusions: 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.

背景:基因逆转录拷贝(retrocopies)已成为进化新颖性的主要来源。MicroRNAs (miRNAs)是一种小而高度保守的RNA分子,是基因表达的关键转录后调节因子。mirna的起源和随后的进化已经被解决,但尚未完全阐明。结果:在这项研究中,我们通过逆转录mRNA序列(retro-miRs)对miRNA的起源进行了全面的研究。我们从mRNA逆转录拷贝中鉴定出17个逆转录mirs。这些逆转录mirna中有4个在逆转录序列中从头开始,而13个逆转录mirna位于外显子区域,并与其宿主mrna一起复制。我们发现逆转录mirs具有灵长类特异性,包括5个在所有灵长类动物中保守的逆转录mirs和2个人类特异性的逆转录mirs。除miR-10527外,所有逆转录mirs均表达了预测和实验验证的靶基因。值得注意的是,逆转录mirs的靶基因参与了关键的生物学过程,如代谢过程、细胞信号传导和中枢神经系统神经递质的调节。此外,我们发现这些逆转录mirs通过靶向关键的癌症基因在癌症中发挥潜在的致癌作用,并在几种癌症类型中过度表达,包括肝细胞癌和胃腺癌。结论:我们的研究结果表明,mRNA逆转录转位是灵长类动物产生新型mirna(逆转录- mirs)的关键机制。这些逆转录mirs是表达的,保守的,具有重要细胞功能的靶基因,在癌症中发挥重要作用。
{"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 Q1 GENETICS & HEREDITY 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

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.

越来越多的证据表明,内源性逆转录病毒(erv)在宿主对感染的反应和疾病的发展中起着重要作用。通过分析chip测序数据集,我们发现SARS-CoV-2感染诱导erv LTR69亚家族中几个位点的H3K27乙酰化。通过功能分析,我们确定了一个sars - cov -2激活的LTR69位点,称为Dup69,它具有调节活性,并对转录因子IRF3和p65/RELA有反应。LTR69_Dup69位于长链非编码RNA基因(ENSG00000289418)上游约500 bp,位于编码糖尿病相关自身抗原的PTPRN2基因内。ENSG00000289418和PTPRN2在SARS-CoV-2感染后表达显著增加。因此,我们的研究揭示了外源性病毒与内源性病毒的相互作用,并有助于理解erv在感染过程中如何调节基因表达。
{"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 Q1 GENETICS & HEREDITY Pub Date : 2023-09-02 DOI: 10.1186/s13100-023-00298-2
Zuzana Loubalova, Parthena Konstantinidou, Astrid D Haase

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.

piwi相互作用rna (pirna)负责阻止生殖细胞中转座因子的移动并保护种系基因组的完整性。在这篇综述中,我们研究了pirna引导的沉默的共同因素以及在物种之间观察到的差异。我们将piRNA的生物发生机制和功能分为几个模块。单个PIWI蛋白以不同的方式结合这些模块来产生独特的PIWI- pirna通路,然而这些通路具有执行保守功能的能力。这种模块化模型结合了保守的核心机制,并适应了可变的辅助因素。适应性是这种基于rna的免疫系统的标志。我们认为,考虑生殖细胞生物学和常驻转座子在不同生物体中的差异,对于将在piRNA生物学中观察到的变化置于背景中是必不可少的,同时仍然强调支撑这一过程的保守主题。
{"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
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Mobile DNA
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