A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response

Huarte, Maite; Guttman, Mitchell; Feldser, David M.; Garber, Manuel; Koziol, Magdalena J.; Kenzelmann-Broz, Daniela; Khalil, Ahmad M.; Zuk, Or; Amit, Ido; Rabani, Michal; Attardi, Laura D.; Regev, Aviv; Lander, Eric S.; Jacks, Tyler; Rinn, John L.

doi:10.1016/j.cell.2010.06.040

Cited by 1,900 publications

(1,829 citation statements)

References 33 publications

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“…Others guide protein complexes to their correct sub-cellular destination (Huarte et al, 2010) or play structural roles by forming a scaffold for the assembly of cellular sub-compartments (Souquere et al, 2010). In some cases, not even the product but rather the act of transcription itself provides functionality: For instance, deep-sequencing has identified the existence of a class of divergent lncRNAs that are transcribed anti-sense to the promoters of coding genes and provide directionality of coding gene transcription (Almada et al, 2013).…”

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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“…All subjects were genotyped by PCR and ability to local or global regulation of gene expression via epigenetic, transcriptional or post-transcriptional mechanisms [3]. Indeed, several lncRNAs were found to have crucial roles in controlling cellular pathways and gene expression programs, thus impacting the oncogenic processes by presenting either oncogenic or tumor suppressive functions [4]. The HOX Transcript Antisense Intergenic RNA (HOTAIR) is a trans-acting lncRNA able to reprogram chromatin organization throughout the genome, as it is scaffold for the binding of Polycomb Repressive Complex (PRC2) in its 5′ domain, while interacting on the 3′ domain with LSD1/REST/CoREST complex [5,6].…”

Section: Introductionmentioning

confidence: 99%

Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in glioma susceptibility and patient prognosis

et al. 2017

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restriction fragment length polymorphism (RFLP). No statistically significant differences were found in the genotype or allele distributions of either rs920778 or rs12826786 between glioma patients and controls, suggesting these SNPs are not associated with glioma risk. No significant associations were found between rs920778 variants and HOTAIR expression levels, while rs12826786 CT genotype was associated with increased intratumoral HOTAIR RNA levels when compared to TT genotype (p-value = 0.04). Univariate (Log-rank) and multivariate (Cox proportional) analyses showed both rs920778 CT and rs12826786 CT genotypes were significantly associated with longer overall survival of WHO grade III anaplastic oligodendroglioma patients. Our results suggest that HOTAIR SNPs rs920778 and rs12826786 do not play a significant role in glioma susceptibility, but may be important prognostic factors in anaplastic oligodendroglioma patients. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in glioma.

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“…De même, des fonctions oncogéniques ont été suggérées pour plusieurs autres lncRNA dans, entre autres, le cancer du foie (HULC, highly up-regulated in liver cancer) [27], de la prostate (PCA3, prostate cancer antigen 3) [28,29] et du rein (MVIH, microvascular invasion in HCC) [30]. Finalement, certains lncRNA, tels que LincRNA-p21 et Meg3 (maternally expressed 3), ont été impliqués dans la modulation de la réponse p53 [31,32]. La participation des lncRNA au développement de pathologies ne se limite cependant pas aux cancers.…”

Section: Le Rôle Des Lncrna Dans Le Développement Des Maladies Et Desunclassified