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一种内源性逆转录病毒元件利用上游调控序列来实现体细胞表达和移动性。

An endogenous retroviral element co-opts an upstream regulatory sequence to achieve somatic expression and mobility.

作者信息

Rubanova Natalia, Singh Darshika, Barolle Louis, Chalvet Fabienne, Netter Sophie, Poidevin Mickaël, Servant Nicolas, Bardin Allison J, Siudeja Katarzyna

机构信息

Institut Curie, PSL Research Univers ity, CNRS UMR 3215, INSERM U934, Stem Cells and Tissue Homeostasis Group, Paris 75005, France.

Institut Curie Bioinformatics Core Facility, PSL Research University, INSERM U900, MINES ParisTech, Paris 75005, France.

出版信息

Nucleic Acids Res. 2025 Jun 6;53(11). doi: 10.1093/nar/gkaf485.

Abstract

Retrotransposons, multi-copy sequences that propagate via copy-and-paste mechanisms, occupy large portions of eukaryotic genomes. A great majority of their manifold copies remain silenced in somatic cells; nevertheless, some are transcribed, often in a tissue-specific manner, and a small fraction retains its ability to mobilize. While it is well characterized that retrotransposon sequences may provide cis-regulatory elements for neighboring genes, how their own expression and mobility are achieved is not well understood. Here, using long-read DNA sequencing, we characterize somatic retrotransposition in the Drosophila intestine. We show that retroelement mobility does not change significantly upon aging and is limited to very few active sub-families. Importantly, we identify a donor locus of an endogenous LTR (long terminal repeat) retroviral element rover, active in the intestinal tissue. We reveal that gut activity of the rover donor copy depends on its genomic environment. Without affecting local gene expression, the copy co-opts its upstream genomic sequence, rich in transcription factor binding sites, for somatic expression. Further, we show that escargot, a snail-type transcription factor, can drive transcriptional activity of the active rover copy. These data provide new insights into how locus-specific features allow active retrotransposons to produce functional transcripts and mobilize in a somatic lineage.

摘要

逆转录转座子是通过复制粘贴机制进行传播的多拷贝序列,占据了真核生物基因组的很大一部分。它们的大量拷贝在体细胞中大多保持沉默;然而,有些拷贝会被转录,通常是以组织特异性的方式,并且一小部分仍保留其移动能力。虽然逆转录转座子序列可能为邻近基因提供顺式调控元件这一点已得到充分表征,但它们自身的表达和移动是如何实现的却尚未得到很好的理解。在这里,我们使用长读长DNA测序技术,对果蝇肠道中的体细胞逆转录转座进行了表征。我们发现,逆转录元件的移动性在衰老过程中没有显著变化,并且仅限于极少数活跃的亚家族。重要的是,我们确定了一个在肠道组织中活跃的内源性LTR(长末端重复序列)逆转录病毒元件rover的供体位点。我们揭示,rover供体拷贝在肠道中的活性取决于其基因组环境。在不影响局部基因表达的情况下,该拷贝利用其富含转录因子结合位点的上游基因组序列进行体细胞表达。此外,我们表明,蜗牛型转录因子esg可以驱动活跃的rover拷贝的转录活性。这些数据为位点特异性特征如何使活跃的逆转录转座子产生功能性转录本并在体细胞谱系中移动提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd9b/12168068/8227c90bf099/gkaf485figgra1.jpg

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