Non-polyadenylated transcription in embryonic stem cells reveals novel non-coding RNA related to pluripotency and differentiation

Livyatan, Ilana; Harikumar, Arigela; Nissim-Rafinia, Malka; Duttagupta, Radharani; Gingeras, T; Meshorer, Eran

doi:10.1093/nar/gkt316

Cited by 28 publications

(25 citation statements)

References 78 publications

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“…For example, small non-polyadenylated (NPA)–conserved RNA (snacRNA) differs significantly between embryonic stem cells and differentiated cells[120]. It is unknown whether snacRNAs have functional activity in cancer cells or CSCs.…”

Section: Other Ncrna Species In Cancer Cells and Cscsmentioning

confidence: 99%

Noncoding RNAs in cancer and cancer stem cells

Huang¹,

Alvarez²,

Hu³

et al. 2013

Chin J Cancer

129

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In recent years, it has become increasingly apparent that noncoding RNAs (ncRNA) are of crucial importance for human cancer. The functional relevance of ncRNAs is particularly evident for microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). miRNAs are endogenously expressed small RNA sequences that act as post-transcriptional regulators of gene expression and have been extensively studied for their roles in cancers, whereas lncRNAs are emerging as important players in the cancer paradigm in recent years. These noncoding genes are often aberrantly expressed in a variety of human cancers. However, the biological functions of most ncRNAs remain largely unknown. Recently, evidence has begun to accumulate describing how ncRNAs are dysregulated in cancer and cancer stem cells, a subset of cancer cells harboring self-renewal and differentiation capacities. These studies provide insight into the functional roles that ncRNAs play in tumor initiation, progression, and resistance to therapies, and they suggest ncRNAs as attractive therapeutic targets and potentially useful diagnostic tools.

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Section: Other Ncrna Species In Cancer Cells and Cscsmentioning

confidence: 99%

Noncoding RNAs in cancer and cancer stem cells

Huang¹,

Alvarez²,

Hu³

et al. 2013

Chin J Cancer

129

View full text Add to dashboard Cite

show abstract

“…Two major discoveries over the last ten years challenge this decades-old concept. First, genome-wide RNA expression studies show widespread transcription across the mouse and human genomes with roughly equal amounts of polyadenylated and nonpolyadenylated RNA 2–7 . Second, the combined efforts of the ENC yclopedia O f D NA E lements (ENCODE) Consortium and many other labs have revealed the existence of millions of codes that punctuate the human genome, most notably codes for transcription factor binding 8–12 .…”

Section: Introductionmentioning

confidence: 99%

Identification and Initial Functional Characterization of a Human Vascular Cell–Enriched Long Noncoding RNA

Bell

Long

Lin

et al. 2014

ATVB

259

228

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Objective Long non-coding RNAs (lncRNAs) represent a rapidly growing class of RNA genes with functions related primarily to transcriptional and post-transcriptional control of gene expression. There is a paucity of information about lncRNA expression and function in human vascular cells. Thus, we set out to identify novel lncRNA genes in human vascular smooth muscle cells and to gain insight into their role in the control of smooth muscle cell phenotypes. Approach and Results RNA-sequencing of human coronary artery smooth muscle cells revealed 31 unannotated lncRNAs, including a vascular cell-enriched lncRNA we call SENCR (Smooth muscle and Endothelial cell enriched migration/differentiation-associated long Non-Coding RNA). Strand-specific RT-PCR and rapid amplification of cDNA ends indicate that SENCR is transcribed antisense from the 5’ end of the FLI1 gene and exists as two splice variants. RNA fluorescence in situ hybridization and biochemical fractionation studies demonstrate SENCR is a cytoplasmic lncRNA. Consistent with this observation, knockdown studies reveal little to no cis-acting effect of SENCR on FLI1 or neighboring gene expression. RNA-sequencing experiments in smooth muscle cells following SENCR knockdown disclose decreased expression of Myocardin and numerous smooth muscle contractile genes, while a number of pro-migratory genes are increased. RT-PCR and Western blotting experiments validate several differentially expressed genes following SENCR knockdown. Loss-of-function studies in scratch wound and Boyden chamber assays support SENCR as an inhibitor of smooth muscle cell migration. Conclusion SENCR is a new vascular cell-enriched, cytoplasmic lncRNA that appears to stabilize the smooth muscle cell contractile phenotype.

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“…4C) and previous reports indicating the presence of intron-derived non-coding RNAs. [37][38][39][40] Finally, RNAomeSeq is highly strand specific (99.8% correct orientation; Table S5). Using strand-specificity sequence information intrinsic to the RNAomeSeq method, we regularly observed intronic reads expressed from the opposite strand compared to gene orientation, strongly indicating the presence of a non-coding RNA encoded in the intron.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the RNA landscape by RNAome sequencing

et al. 2015

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Current RNA expression profiling methods rely on enrichment steps for specific RNA classes, thereby not detecting all RNA species in an unperturbed manner. We report strand-specific RNAome sequencing that determines expression of small and large RNAs from rRNA-depleted total RNA in a single sequence run. Since current analysis pipelines cannot reliably analyze small and large RNAs simultaneously, we developed TRAP, Total Rna Analysis Pipeline, a robust interface that is also compatible with existing RNA sequencing protocols. RNAome sequencing quantitatively preserved all RNA classes, allowing cross-class comparisons that facilitates the identification of relationships between different RNA classes. We demonstrate the strength of RNAome sequencing in mouse embryonic stem cells treated with cisplatin. MicroRNA and mRNA expression in RNAome sequencing significantly correlated between replicates and was in concordance with both existing RNA sequencing methods and gene expression arrays generated from the same samples. Moreover, RNAome sequencing also detected additional RNA classes such as enhancer RNAs, anti-sense RNAs, novel RNA species and numerous differentially expressed RNAs undetectable by other methods. At the level of complete RNA classes, RNAome sequencing also identified a specific global repression of the microRNA and microRNA isoform classes after cisplatin treatment whereas all other classes such as mRNAs were unchanged. These characteristics of RNAome sequencing will significantly improve expression analysis as well as studies on RNA biology not covered by existing methods.

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Non-polyadenylated transcription in embryonic stem cells reveals novel non-coding RNA related to pluripotency and differentiation

Cited by 28 publications

References 78 publications

Noncoding RNAs in cancer and cancer stem cells

Noncoding RNAs in cancer and cancer stem cells

Identification and Initial Functional Characterization of a Human Vascular Cell–Enriched Long Noncoding RNA

Deciphering the RNA landscape by RNAome sequencing

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