Transposable element sequence fragments incorporated into coding and noncoding transcripts modulate the transcriptome of human pluripotent stem cells

被引：27

作者：

Babarinde, Isaac A. ^{[1
,2
]}

Ma, Gang ^{[1
,2
]}

Li, Yuhao ^{[1
,2
]}

Deng, Boping ^{[2
,3
]}

Luo, Zhiwei ^{[4
,5
,6
]}

Liu, Hao ^{[4
,5
,6
]}

Abdul, Mazid Md ^{[4
,5
,6
]}

Ward, Carl ^{[4
,5
,6
]}

Chen, Minchun ^{[2
]}

Fu, Xiuling ^{[1
,2
]}

Shi, Liyang ^{[1
,2
]}

Duttlinger, Martha ^{[2
]}

He, Jiangping ^{[7
]}

Sun, Li ^{[1
,2
]}

Li, Wenjuan ^{[4
,5
,6
]}

Zhuang, Qiang ^{[2
]}

Tong, Guoqing ^{[8
]}

Frampton, Jon ^{[3
]}

Cazier, Jean-Baptiste ^{[3
,9
]}

Chen, Jiekai ^{[5
,6
,7
,10
,11
]}

Jauch, Ralf ^{[12
]}

Esteban, Miguel A. ^{[4
,5
,6
,13
]}

Hutchins, Andrew P. ^{[1
,2
]}

机构：

[1] Southern Univ Sci & Technol, Sch Life Sci, Shenzhen Key Lab Gene Regulat & Syst Biol, Shenzhen 518055, Peoples R China

[2] Southern Univ Sci & Technol, Sch Life Sci, Dept Biol, Shenzhen 518055, Peoples R China

[3] Univ Birmingham, Inst Canc & Genom Sci, Birmingham B15 2TT, W Midlands, England

[4] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Lab Integrat Biol, Guangzhou 510530, Peoples R China

[5] Chinese Acad Sci, Key Lab Regenerat Biol, Guangzhou 510530, Peoples R China

[6] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Stem Cell & Regenerat Med, Guangzhou 510530, Peoples R China

[7] Ctr Cell Lineage & Atlas CCLA, Bioland Lab, Guangzhou Regenerat Med & Hlth Guangdong Lab, Guangzhou 510005, Peoples R China

[8] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Ctr Reprod Med, Shanghai 200120, Peoples R China

[9] Univ Birmingham, Ctr Computat Biol, Birmingham, W Midlands, England

[10] Guangzhou Med Univ, Joint Sch Life Sci, Guangzhou, Peoples R China

[11] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou, Peoples R China

[12] Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China

[13] Guangzhou Regenerat Med & Hlth Guangdong Lab, Bioland Lab, Guangzhou 510005, Peoples R China

来源：

NUCLEIC ACIDS RESEARCH | 2021年 / 49卷 / 16期

基金：

中国国家自然科学基金;

关键词：

MESSENGER-RNA DECAY; EXPRESSION; ALIGNMENT; GENOME; RETROTRANSPOSONS; QUANTIFICATION; RECONSTRUCTION; PROGENITOR; CHROMATIN; EVOLUTION;

D O I：

10.1093/nar/gkab710

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 tran- script 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.

引用

页码：9132 / 9153

页数：22

共 106 条

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