VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and cancer

Genome Biology

Philipp Kapranov⁴  Weidong Xiao⁸  Timothy A McCaffrey¹  Timothy J Triche⁶  Nianli Sang³  Estelle Nicolas⁷  Sandra Lazorthes⁷  Xiaoxuan Fan⁸  Michael R Tackett⁴  Biao Dong⁸  Dmitry Shtokalo²  Georges St Laurent⁵ 

[1] The George Washington University Medical Center, Department of Medicine, Division of Genomic Medicine, 2300 I St. NW, Washington, D.C;A.P.Ershov Institute of Informatics Systems SB RAS, 6, Acad. Lavrentjev ave., Novosibirsk 630090, Russia;Department of Biology, Drexel University, 3245 Chestnut St, PISB 417, Philadelphia, PA;St. Laurent Institute, One Kendall Square, Cambridge, MA;Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI;Department of Pathology, University of Southern California, 1975 Zonal Avenue, Los Angeles, CA;CNRS, LBCMCP, F-31062 Toulouse, France;Department of Microbiology and Immunology, Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, PA

关键词: RNAseq;    single molecule sequencing;    intelligent scaffold;    non-coding RNA;    embryonic stem cell;    cancer;    macroRNA;    LTR;    vlincRNA;   

Others  :  864148
DOI  :  10.1186/gb-2013-14-7-r73

 received in 2012-11-05, accepted in 2013-07-22,  发布年份 2013

【 摘 要 】

Background

The function of the non-coding portion of the human genome remains one of the most important questions of our time. Its vast complexity is exemplified by the recent identification of an unusual and notable component of the transcriptome - very long intergenic non-coding RNAs, termed vlincRNAs.

Results

Here we identify 2,147 vlincRNAs covering 10 percent of our genome. We show they are present not only in cancerous cells, but also in primary cells and normal human tissues, and are controlled by canonical promoters. Furthermore, vlincRNA promoters frequently originate from within endogenous retroviral sequences. Strikingly, the number of vlincRNAs expressed from endogenous retroviral promoters strongly correlates with pluripotency or the degree of malignant transformation. These results suggest a previously unknown connection between the pluripotent state and cancer via retroviral repeat-driven expression of vlincRNAs. Finally, we show that vlincRNAs can be syntenically conserved in humans and mouse and their depletion using RNAi can cause apoptosis in cancerous cells.

Conclusions

These intriguing observations suggest that vlincRNAs could create a framework that combines many existing short ESTs and lincRNAs into a landscape of very long transcripts functioning in the regulation of gene expression in the nucleus. Certain types of vlincRNAs participate at specific stages of normal development and, based on analysis of a limited set of cancerous and primary cell lines, they appear to be co-opted by cancer-associated transcriptional programs. This provides additional understanding of transcriptome regulation during the malignant state, and could lead to additional targets and options for its reversal.

【 授权许可】

   
2013 St Laurent et al.; licensee BioMed Central Ltd.

【 图 表 】

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