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RNA m6A modification orchestrates a LINE-1–host interaction that facilitates retrotransposition and contributes to long gene vulnerability

机译:RNA M6A修改协调了一个线-1-宿主交互便于转回散退并有助于长期漏洞

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摘要

a Pie charts showing the genomic distribution of m6A peaks on non-LTR (LINE, SINE) and LTR retrotransposon elements based on K562 MINT-Seq. Left, Genomic distribution of MINT-Seq m6A peaks. Right, Expected distribution of MINT-Seq m6A peaks. These expected percentages were calculated based on a null hypothesis that any transcribed regions in the genome have equal chances to contain m6A peaks. Thus, from the TT-Seq reads mapped to LINE, SINE, and LTR elements in the reference genome (hg19), we can deduce the peaks to be expected from these regions. b A snapshot of genome browser tracks of TT-Seq, MINT-Seq, H3K36me3 ChIP-Seq data in K562 cells, together with the LINE and gene annotations in genome hg19 (below the tracks). RefSeq RNA gene LINC00534 is shown that it contains many strong intronic m6A peaks perfectly overlapping L1s (arrows). (+) and (−) in the data tracks indicate Watson and Crick strands. c A bar plot showing numbers of intronic L1s that are sense- (blue) or antisense- (green) oriented to the hosting genes. The “Expected” denote numbers calculated using all intronic L1s, while “Observed” using intronic L1s overlapping m6A MINT-Seq peaks. P-value was calculated with Fisher’s exact test. d A density plot showing the percentage of L1 distribution based on the length of all hg19 annotated L1s (gray) or of the m6A-marked L1s (red). e A plot showing relative m6A levels (MINT-Seq/TT-Seq) across all MILs (intronic L1s that overlap MINT-Seq peaks). A subset of MILs harboring exceptionally high levels of m6A was identified as Super-MILs (n = 393), achieved by using the slope of the distribution curve (blue line and green point indicate the boundary between Super-MILs and Typical MILs). f–h Boxplots showing features of Super-MILs, Typical MILs and the Control L1s (transcribed intronic L1s without m6A peaks), in terms of sequence divergence as compared to L1 consensus (f), length (g) and m6A motif (RRACH) density (h). P-values were calculated with Mann-Whitney U tests. i, j Boxplots of the same three groups of L1s as in the previous panels, showing their transcript levels (i), and relative RNA stability (calculated by taking the ratio between RNA-Seq and TT-Seq FPKM, panel j). P-values were calculated with Mann–Whitney U tests.
机译:基于K562 MINT-SEQ的非LTR(线路,正弦)和LTR回收转换元素的M6a峰的基因组分布的饼图。左,薄荷SEQ M6A峰的基因组分布。右,预期的薄荷SEQ M6A峰的分布。这些预期的百分比是基于零假设来计算的,即基因组中的任何转录区域具有相同的机理含有M6A峰。因此,从参考基因组(HG19)中的TT-SEQ读取映射到线,正弦和LTR元素,我们可以推断出这些区域预期的峰值。 b TT-SEQ,MINT-SEQ,H3K36ME3芯片-SEQ-SEQ数据的基因组浏览器轨道的快照以及基因组HG19中的线和基因注释(在轨道下方)。 Refseq RNA Gene LINC00534示出认为它含有许多强的内肠杆菌M6a峰值完全重叠L1s(箭头)。 (+)和( - )在数据轨道中表示Watson和Crick Strands。 c显示归属于托管基因的感觉 - (蓝色)或反义 - (绿色)的内血管内部L1的条形图。 “预期”表示使用所有内部L1S计算的数量,同时使用内肠杆菌L1s重叠M6a Mint-SEQ峰值“观察”。使用Fisher的确切测试计算p值。 D基于所有HG19带注释的L1S(灰色)或M6A标记的L1S(红色)的长度表示L1分布百分比的密度图。在所有密耳中显示相对M6a水平(MINT-SEQ / TT-SEQ)的图(重叠MINT-SEQ峰值的内部L1)。通过使用分布曲线的斜率(蓝线和绿点表示超级密耳和典型密耳之间的边界,鉴定为超级密耳(n = 393)的米尔群体被鉴定为超级密耳(n = 393)。与L1共有(f),长度(g)和m6a主题(RRACH)相比,序列发散的序列发散方面显示超级密耳,典型密耳和控制L1s的特征(典型的米尔和没有M6a峰的转录内肠L1s)的特征。密度(h)。用Mann-Whitney U测试计算p值。 I,J Boxplots的三组L1S在前面的面板中,显示其转录水平(I)和相对RNA稳定性(通过在RNA-SEQ和TT-SEQ FPKM,Panel J)之间计算。用Mann-Whitney U测试计算p值。

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