RIP-seq reveals LINE-1 ORF1p association with p-body enriched mRNAs.
RIP-seq reveals LINE-1 ORF1p association with p-body enriched mRNAs.
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DOI：
10.1186/s13100-021-00233-3
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发表时间：
2021-02-09
期刊：
影响因子：
4.9
通讯作者：
Fenyö D
中科院分区：
文献类型：
--
作者：
Briggs EM;McKerrow W;Mita P;Boeke JD;Logan SK;Fenyö D
长穿插元件-1 （LINE-1）是一种自主的逆转录元件，能够通过称为逆转录转座的过程将自身“复制粘贴”到宿主基因组的新位点上。LINE-1双链mRNA编码两种蛋白，ORF1p是一种核酸伴侣蛋白，ORF2p是一种具有核酸内切酶和逆转录酶活性的蛋白。这两种蛋白都以顺式结合LINE-1 mRNA，并且是逆转录所必需的。虽然在大多数健康体细胞中，LINE-1转录通常通过多种机制受到抑制，但在近50%的肿瘤中观察到ORF1p表达，并且在包括前列腺癌在内的类似肿瘤中记录了新的LINE-1插入。在这里，我们利用RNA免疫沉淀（RIP）和L1EM分析软件鉴定前列腺癌细胞中ORF1p结合的RNA。我们鉴定了在亲本雄激素敏感和雄激素非依赖性克隆衍生物中表达的LINE-1位点。在所有不依赖雄激素的细胞中，我们发现了更高水平的LINE-1 RNA，以及LINE-1位点的独特表达模式。有趣的是，我们观察到ORF1p在所有评估的前列腺癌细胞系中结合了许多non-LINE-1 mRNA， polyA RNA和定位于p小体的RNA尤其富集。此外，ORF1p RIP中鉴定的rna表达水平与癌症基因组图谱（TCGA）中LINE-1阳性肿瘤中表达的rna相关。我们的研究结果显示，与亲代雄激素依赖性细胞相比，雄激素非依赖性细胞系的LINE-1基因座表达有显著的重塑。此外，我们发现ORF1p结合了大量的非LINE-1 mRNA，并且富集的ORF1p结合mRNA在表达TCGA的LINE-1前列腺肿瘤中也被扩增，这表明我们的发现与前列腺癌的生物学相关性。在线版本包含补充材料，可在10.1186/s13100-021-00233-3获得。
Long INterspersed Element-1 (LINE-1) is an autonomous retroelement able to “copy-and-paste” itself into new loci of the host genome through a process called retrotransposition. The LINE-1 bicistronic mRNA codes for two proteins, ORF1p, a nucleic acid chaperone, and ORF2p, a protein with endonuclease and reverse transcriptase activity. Both proteins bind LINE-1 mRNA in cis and are necessary for retrotransposition. While LINE-1 transcription is usually repressed in most healthy somatic cells through a plethora of mechanisms, ORF1p expression has been observed in nearly 50% of tumors, and new LINE-1 insertions have been documented in a similar fraction of tumors, including prostate cancer. Here, we utilized RNA ImmunoPrecipitation (RIP) and the L1EM analysis software to identify ORF1p bound RNA in prostate cancer cells. We identified LINE-1 loci that were expressed in parental androgen sensitive and androgen independent clonal derivatives. In all androgen independent cells, we found higher levels of LINE-1 RNA, as well as unique expression patterns of LINE-1 loci. Interestingly, we observed that ORF1p bound many non-LINE-1 mRNA in all prostate cancer cell lines evaluated, and polyA RNA, and RNA localized in p-bodies were especially enriched. Furthermore, the expression levels of RNAs identified in our ORF1p RIP correlated with RNAs expressed in LINE-1 positive tumors from The Cancer Genome Atlas (TCGA). Our results show a significant remodeling of LINE-1 loci expression in androgen independent cell lines when compared to parental androgen dependent cells. Additionally, we found that ORF1p bound a significant amount of non-LINE-1 mRNA, and that the enriched ORF1p bound mRNAs are also amplified in LINE-1 expressing TCGA prostate tumors, indicating the biological relevance of our findings to prostate cancer. The online version contains supplementary material available at 10.1186/s13100-021-00233-3.
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Brouha, B;Schustak, J;Kazazian, HH
通讯作者：
Kazazian, HH
影响因子：
30.8
作者：
Dewannieux, M;Esnault, C;Heidmann, T
通讯作者：
Heidmann, T
影响因子：
3.7
作者：
Chen, Long;Dahlstrom, Jane E.;Rangasamy, Danny
通讯作者：
Rangasamy, Danny