Transposable element sequence fragments incorporated into coding and noncoding transcripts modulate the transcriptome of human pluripotent stem cells.
Transposable element sequence fragments incorporated into coding and noncoding transcripts modulate the transcriptome of human pluripotent stem cells.
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DOI：
10.1093/nar/gkab710
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发表时间：
2021-09-20
影响因子：
14.9
通讯作者：
Hutchins AP
中科院分区：
文献类型：
--
作者：
Babarinde IA;Ma G;Li Y;Deng B;Luo Z;Liu H;Abdul MM;Ward C;Chen M;Fu X;Shi L;Duttlinger M;He J;Sun L;Li W;Zhuang Q;Tong G;Frampton J;Cazier JB;Chen J;Jauch R;Esteban MA;Hutchins AP
转座因子（te）占哺乳动物基因组的近40%，虽然大多数是片段的，不再能够转座，但它们仍然可以促进细胞功能。由RNA聚合酶II转录的基因中的TEs可以作为初级转录物的一部分被复制；然而，它们对成熟转录序列的全部贡献仍未得到解决。在这里，使用长读和短读（LR和SR） RNA测序数据，我们发现人类多能干细胞（hPSCs）中26%的编码转录本和65%的非编码转录本包含te衍生序列。不同的TE家族以独特的模式被整合到rna中，从而影响转录本的结构和功能。转录物中TE序列的存在与TE型亚细胞分布的特异性变化、稳态水平和半衰期的改变以及与RNA结合蛋白（rbp）的差异关联相关。我们发现内源性逆转录病毒（ERVs）和LINE:L1与hpsc特异性结合进入蛋白质编码mrna，产生TE序列衍生的肽。最后，单细胞RNA-seq显示，hPSCs表达含有erv的转录物，而分化亚群缺乏erv，表达SINE和LINE-containing转录物。总的来说，我们的综合分析表明，将TE序列结合到hPSCs的rna中比以前认为的更广泛，影响更大。
Transposable elements (TEs) occupy nearly 40% of mammalian genomes and, whilst most are fragmentary and no longer capable of transposition, they can nevertheless contribute to cell function. TEs within genes transcribed by RNA polymerase II can be copied as parts of primary transcripts; however, their full contribution to mature transcript sequences remains unresolved. Here, using long and short read (LR and SR) RNA sequencing data, we show that 26% of coding and 65% of noncoding transcripts in human pluripotent stem cells (hPSCs) contain TE-derived sequences. Different TE families are incorporated into RNAs in unique patterns, with consequences to transcript structure and function. The presence of TE sequences within a transcript is correlated with TE-type specific changes in its subcellular distribution, alterations in steady-state levels and half-life, and differential association with RNA Binding Proteins (RBPs). We identify hPSC-specific incorporation of endogenous retroviruses (ERVs) and LINE:L1 into protein-coding mRNAs, which generate TE sequence-derived peptides. Finally, single cell RNA-seq reveals that hPSCs express ERV-containing transcripts, whilst differentiating subpopulations lack ERVs and express SINE and LINE-containing transcripts. Overall, our comprehensive analysis demonstrates that the incorporation of TE sequences into the RNAs of hPSCs is more widespread and has a greater impact than previously appreciated.
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影响因子：
5.8
作者：
Barnett, Derek W.;Garrison, Erik K.;Marth, Gabor T.
通讯作者：
Marth, Gabor T.
影响因子：
64.5
作者：
Attig J;Agostini F;Gooding C;Chakrabarti AM;Singh A;Haberman N;Zagalak JA;Emmett W;Smith CWJ;Luscombe NM;Ule J
通讯作者：
Ule J
影响因子：
3.3
作者：
Fuchs NV;Loewer S;Daley GQ;Izsvák Z;Löwer J;Löwer R
通讯作者：
Löwer R
DOI：
10.1098/rstb.2019.0342
发表时间：
2020-03-30
影响因子：
6.3
作者：
Clayton, Evan A.;Rishishwar, Lavanya;Jordan, I. King
通讯作者：
Jordan, I. King
影响因子：
64.8
作者：
Gong, Chenguang;Maquat, Lynne E.
通讯作者：
Maquat, Lynne E.