Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters

Hung, Tiffany; Wang, Yulei; Lin, Michael; Koegel, Ashley K.; Kotake, Yojiro; Grant, Gavin D.; Horlings, Hugo M.; Shah, Nilay; Umbricht, Christopher B.; Wang, Pei; Wang, Yu; Kong, Benjamin Y.; Langerød, Anita; Børresen-Dale, Anne Lise; Kim, Seung K.; Vijver, Marc J. van de; Sukumar, Saraswati; Whitfield, Michael L.; Kellis, M; Xiong, Yue; Wong, D.; Chang, Howard Y.

doi:10.1038/ng.848

Cited by 1,071 publications

(963 citation statements)

References 51 publications

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“…Likewise, the reported modes of action for this transcript class differ substantially: An emerging theme in lncRNA-mediated control of gene expression, however, seems to be the recruitment of histonemodifying complexes to specific loci in the genome to epigenetically regulate target gene transcription (Mercer and Mattick, 2013;Rinn, 2014). For several further lncRNAs, however, other functions have been reported: Some representatives act as decoys by titrating transcription factors and thus, indirectly regulate target gene transcription (Hung et al, 2011).…”

Section: Eukaryotic Long Non-coding Rnas (Lncrnas)mentioning

confidence: 99%

Dual RNA-seq of pathogen and host

2012

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SummaryThe infection of a eukaryotic host cell by a bacterial pathogen is one of the most intimate examples of cross-kingdom interactions in biology. Infection processes are highly relevant from both a basic research as well as a clinical point of view. Sophisticated mechanisms have evolved in the pathogen to manipulate the host response and vice versa host cells have developed a wide range of anti-microbial defense strategies to combat bacterial invasion and clear infections.However, it is this diversity and complexity that makes infection research so challenging to technically address as common approaches have either been optimized for bacterial or eukaryotic organisms. Instead, methods are required that are able to deal with the often dramatic discrepancy between host and pathogen with respect to various cellular properties and processes. One class of cellular macromolecules that exemplify this host-pathogen heterogeneity is given by their transcriptomes: Bacterial transcripts differ from their eukaryotic counterparts in many aspects that involve both quantitative and qualitative traits. The entity of RNA transcripts present in a cell is of paramount interest as it reflects the cell's physiological state under the given condition. Genome-wide transcriptomic techniques such as RNA-seq have therefore been used for single-organism analyses for several years, but their applicability has been limited for infection studies.The present work describes the establishment of a novel transcriptomic approach for infection biology which we have termed "Dual RNA-seq". Using this technology, it was intended to shed light particularly on the contribution of non-protein-encoding transcripts to virulence, as these classes have mostly evaded previous infection studies due to the lack of suitable methods. The performance of Dual RNA-seq was evaluated in an in vitro infection model based on the important facultative intracellular pathogen Salmonella enterica serovar Typhimurium and different human cell lines. Dual RNA-seq was found to be capable of capturing all major bacterial and human transcript classes and proved reproducible. During the course of these experiments, a previously largely uncharacterized bacterial small non-coding RNA (sRNA), referred to as STnc440, was identified as one of the most strongly induced genes in intracellular Salmonella.Interestingly, while inhibition of STnc440 expression has been previously shown to cause a virulence defect in different animal models of Salmonellosis, the underlying molecular mechanisms have remained obscure. Here, classical genetics, transcriptomics and biochemical assays proposed a complex model of Salmonella gene expression control that is orchestrated by this sRNA. In particular, STnc440 was found to be involved in the regulation of multiple bacterial target mRNAs by direct base pair interaction with consequences for Salmonella virulence and

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Section: Eukaryotic Long Non-coding Rnas (Lncrnas)mentioning

confidence: 99%

Dual RNA-seq of pathogen and host

2012

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“…Other studies have inferred and tested the functional role of lincRNAs in processes such as pluripotency and p53 response pathways by associating the expression of lincRNAs with those of protein-coding genes (Guttman et al 2009;Huarte et al 2010;Loewer et al 2010;Hung et al 2011). More globally, a recent comprehensive screen identified dozens of lincRNAs required to maintain pluripotency and suggested that these lincRNAs work in trans .…”

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confidence: 99%

Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses

Cabili¹,

Trapnell²,

Goff³

et al. 2011

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Large intergenic noncoding RNAs (lincRNAs) are emerging as key regulators of diverse cellular processes. Determining the function of individual lincRNAs remains a challenge. Recent advances in RNA sequencing (RNA-seq) and computational methods allow for an unprecedented analysis of such transcripts. Here, we present an integrative approach to define a reference catalog of >8000 human lincRNAs. Our catalog unifies previously existing annotation sources with transcripts we assembled from RNA-seq data collected from~4 billion RNA-seq reads across 24 tissues and cell types. We characterize each lincRNA by a panorama of >30 properties, including sequence, structural, transcriptional, and orthology features. We found that lincRNA expression is strikingly tissue-specific compared with coding genes, and that lincRNAs are typically coexpressed with their neighboring genes, albeit to an extent similar to that of pairs of neighboring protein-coding genes. We distinguish an additional subset of transcripts that have high evolutionary conservation but may include short ORFs and may serve as either lincRNAs or small peptides. Our integrated, comprehensive, yet conservative reference catalog of human lincRNAs reveals the global properties of lincRNAs and will facilitate experimental studies and further functional classification of these genes.

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“…For example, several lncRNAs have been shown to interact with and modulate the activity of the chromatin modifying machinery (Rinn et al 2007;Nagano et al 2008;Pandey et al 2008;Zhao et al 2008Zhao et al , 2010Khalil et al 2009;Huarte et al 2010;Tian et al 2010;Tsai et al 2010;Guttman et al 2011;. Other lncRNAs may act as decoys in the sequestration of miRNAs (Poliseno et al 2010), transcription factors (Hung et al 2011), or other proteins (Tripathi et al 2010). Yet others may serve as precursors for the generation of sRNAs (Kapranov et al 2007;Wilusz et al 2008;Fejes-Toth et al 2009).…”

mentioning

confidence: 99%

Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis

Pauli¹,

Valen²,

Lin³

et al. 2011

Genome Res.

738

830

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Long noncoding RNAs (lncRNAs) comprise a diverse class of transcripts that structurally resemble mRNAs but do not encode proteins. Recent genome-wide studies in humans and the mouse have annotated lncRNAs expressed in cell lines and adult tissues, but a systematic analysis of lncRNAs expressed during vertebrate embryogenesis has been elusive. To identify lncRNAs with potential functions in vertebrate embryogenesis, we performed a time-series of RNA-seq experiments at eight stages during early zebrafish development. We reconstructed 56,535 high-confidence transcripts in 28,912 loci, recovering the vast majority of expressed RefSeq transcripts while identifying thousands of novel isoforms and expressed loci. We defined a stringent set of 1133 noncoding multi-exonic transcripts expressed during embryogenesis. These include long intergenic ncRNAs (lincRNAs), intronic overlapping lncRNAs, exonic antisense overlapping lncRNAs, and precursors for small RNAs (sRNAs). Zebrafish lncRNAs share many of the characteristics of their mammalian counterparts: relatively short length, low exon number, low expression, and conservation levels comparable to that of introns. Subsets of lncRNAs carry chromatin signatures characteristic of genes with developmental functions. The temporal expression profile of lncRNAs revealed two novel properties: lncRNAs are expressed in narrower time windows than are protein-coding genes and are specifically enriched in early-stage embryos. In addition, several lncRNAs show tissue-specific expression and distinct subcellular localization patterns. Integrative computational analyses associated individual lncRNAs with specific pathways and functions, ranging from cell cycle regulation to morphogenesis. Our study provides the first systematic identification of lncRNAs in a vertebrate embryo and forms the foundation for future genetic, genomic, and evolutionary studies.

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Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters

Cited by 1,071 publications

References 51 publications

Dual RNA-seq of pathogen and host

Dual RNA-seq of pathogen and host

Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses

Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis

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