Widespread expression of the ancient HERV-K (HML-2) provirus group in normal human tissues.
Widespread expression of the ancient HERV-K (HML-2) provirus group in normal human tissues.
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DOI：
10.1371/journal.pbio.3001826
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发表时间：
2022-10
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
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已知人类内源性逆转录病毒（HERV）转录物在癌症中高度表达，但其在非病变组织中的活性在很大程度上是未知的。使用来自尸检时采样的正常组织的GTEx RNA-seq数据集，我们在来自948个个体的54种不同组织的13，000个不同样本中表征了最近HERV-K（HML-2）前病毒组的个体表达。HML-2的转录本可以在每个组织样品中鉴定，并且在小脑、垂体、睾丸和甲状腺中升高。在1个或多个组织中共表达了37种不同的个体前病毒，代表了所有3个LTR 5亚组。9个前病毒被鉴定为具有长末端重复序列（LTR）驱动的转录，其中7个属于最近的LTR 5 HS亚组。不同亚群的前病毒在组织表达中表现出偏好性，这可能与其LTR中转录因子结合位点的差异有关。前病毒的表达在进化上较老的前病毒与大猩猩或更老的最早共同祖先中更大。HML-2的表达受生物学性别的显著影响，而年龄和死亡时间（哈代评分）的影响不大。含有完整gag、pro和env开放阅读框（ORF）的前病毒在数据集中表达，几乎每个测量的组织都可能表达至少1个完整ORF（gag）。已知人类内源性逆转录病毒（HERV）转录物在癌症中高度表达，但它们在正常组织中的活性如何？这项研究使用了来自非疾病组织部位的大型格克斯数据集中HERV-K RNA表达的独特模式，为HERV-K与我们的灵长类祖先的共同进化及其在人类生物学中的作用提供了新的见解。
Human endogenous retrovirus (HERV) transcripts are known to be highly expressed in cancers, yet their activity in nondiseased tissue is largely unknown. Using the GTEx RNA-seq dataset from normal tissue sampled at autopsy, we characterized individual expression of the recent HERV-K (HML-2) provirus group across 13,000 different samples of 54 different tissues from 948 individuals. HML-2 transcripts could be identified in every tissue sampled and were elevated in the cerebellum, pituitary, testis, and thyroid. A total of 37 different individual proviruses were expressed in 1 or more tissues, representing all 3 LTR5 subgroups. Nine proviruses were identified as having long terminal repeat (LTR)-driven transcription, 7 of which belonged to the most recent LTR5HS subgroup. Proviruses of different subgroups displayed a bias in tissue expression, which may be associated with differences in transcription factor binding sites in their LTRs. Provirus expression was greater in evolutionarily older proviruses with an earliest shared ancestor of gorilla or older. HML-2 expression was significantly affected by biological sex in 1 tissue, while age and timing of death (Hardy score) had little effect. Proviruses containing intact gag, pro, and env open reading frames (ORFs) were expressed in the dataset, with almost every tissue measured potentially expressing at least 1 intact ORF (gag). Human endogenous retrovirus (HERV) transcripts are known to be highly expressed in cancers, but what is their activity in normal tissue? This study uses unique patterns of HERV-K RNA expression in the large GEx dataset from non-diseased tissue sites to provide new insights into both the coevolution of HERV-K with our primate ancestors and their current role in human biology.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
多种影响控制人基因内含子中内源性逆转录病毒的存活模式。
影响因子：
12.3
作者：
van de Lagemaat, Louie N.;Medstrand, Patrik;Mager, Dixie L.
通讯作者：
Mager, Dixie L.
影响因子：
30.8
作者：
Hughes, JF;Coffin, JM
通讯作者：
Coffin, JM
影响因子：
64.8
作者：
Best, S;LeTissier, P;Stoye, JP
通讯作者：
Stoye, JP
影响因子：
4.7
作者：
Hohn O;Hanke K;Bannert N
通讯作者：
Bannert N