Exceptional structured noncoding RNAs revealed by bacterial metagenome analysis

Weinberg, Zasha; Perreault, Jonathan; Meyer, Michelle M.; Breaker, Ronald R.

doi:10.1038/nature08586

Cited by 106 publications

(147 citation statements)

References 61 publications

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“…Indeed, UTRs and a majority of noncoding RNAs produced in eukaryotes are either not conserved or so highly conserved (as is the case for the RB1 5 ′ UTR) that strong covariation signals cannot be derived (Gardner and Giegerich 2004;Stevens et al 2011;Widmann et al 2012). In contrast, alignmentbased structure prediction has identified thousands of conserved secondary structure motifs in prokaryotic genomes (Weinberg et al 2007(Weinberg et al , 2009.…”

Section: Discussionmentioning

confidence: 99%

Multiple conformations are a conserved and regulatory feature of the RB1 5′ UTR

Kutchko

Sanders

Ziehr

et al. 2015

RNA

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Folding to a well-defined conformation is essential for the function of structured ribonucleic acids (RNAs) like the ribosome and tRNA. Structured elements in the untranslated regions (UTRs) of specific messenger RNAs (mRNAs) are known to control expression. The importance of unstructured regions adopting multiple conformations, however, is still poorly understood. High-resolution SHAPE-directed Boltzmann suboptimal sampling of the Homo sapiens Retinoblastoma 1 (RB1) 5 ′ UTR yields three distinct conformations compatible with the experimental data. Private single nucleotide variants (SNVs) identified in two patients with retinoblastoma each collapse the structural ensemble to a single but distinct well-defined conformation. The RB1 5 ′ UTRs from Bos taurus (cow) and Trichechus manatus latirostris (manatee) are divergent in sequence from H. sapiens (human) yet maintain structural compatibility with high-probability base pairs. SHAPE chemical probing of the cow and manatee RB1 5 ′ UTRs reveals that they also adopt multiple conformations. Luciferase reporter assays reveal that 5 ′ UTR mutations alter RB1 expression. In a traditional model of disease, causative SNVs disrupt a key structural element in the RNA. For the subset of patients with heritable retinoblastoma-associated SNVs in the RB1 5 ′ UTR, the absence of multiple structures is likely causative of the cancer. Our data therefore suggest that selective pressure will favor multiple conformations in eukaryotic UTRs to regulate expression.

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Section: Discussionmentioning

confidence: 99%

Multiple conformations are a conserved and regulatory feature of the RB1 5′ UTR

Kutchko

Sanders

Ziehr

et al. 2015

RNA

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“…(Albrecht et al, 2010(Albrecht et al, , 2011Chabelskaya et al, 2014;Chao et al, 2012;Gong et al, 2011;Grieshaber et al, 2006;Mann et al, 2012;Moon et al, 2013;Ortega et al, 2012;PadalonBrauch et al, 2008;Pfeiffer et al, 2007) crRNA, (Bhaya et al, 2011;Heidrich and Vogel, 2013;Sampson et al, 2013;van der Oost et al, 2014) (Georg and Hess, 2011;Giangrossi et al, 2010;GonzaloAsensio et al, 2013;Gottesman and Storz, 2011;Lasa et al, 2011;Lee and Groisman, 2010;Padalon-Brauch et al, 2008;Sesto et al, 2013) circRNAs rare varies arise from the 3'-5' ligation of both ends of linear RNA molecules n. a. -- (Doose et al, 2013;Vicens and Cech, 2009) - (Conway et al, 2014;Weinberg et al, 2009) Carpenter et al, 2013;Gomez et al, 2013;Iiott et al, 2014;Imamura et al, 2014;Li et al, 2014;Rapicavoli et al, 2013) poly ( (Jeck and Sharpless, 2014;Memczak et al, 2013) 1 : in the given context of bacterial infection of eukaryo...…”

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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“…Successful ncRNA searches using these approaches have been reported in Archaea (Klein et al 2002;Schattner 2002), Bacteria Livny et al 2006;Geissmann et al 2009), and Eukaryotes (Mendes et al 2009;Li et al 2010). More recently, the CMfinder tool (Yao et al 2006) was used to predict large sets of new ncRNA/motifs signatures in Bacteria (Weinberg et al 2007(Weinberg et al , 2009). …”

Section: Introductionmentioning

confidence: 99%

RNAspace.org: An integrated environment for the prediction, annotation, and analysis of ncRNA

Cros¹,

Monte²,

Mariette³

et al. 2011

RNA

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The annotation of noncoding RNA genes remains a major bottleneck in genome sequencing projects. Most genome sequences released today still come with sets of tRNAs and rRNAs as the only annotated RNA elements, ignoring hundreds of other RNA families. We have developed a web environment that is dedicated to noncoding RNA (ncRNA) prediction, annotation, and analysis and allows users to run a variety of tools in an integrated and flexible manner. This environment offers complementary ncRNA gene finders and a set of tools for the comparison, visualization, editing, and export of ncRNA candidates. Predictions can be filtered according to a large set of characteristics. Based on this environment, we created a public website located at http://RNAspace.org. It accepts genomic sequences up to 5 Mb, which permits for an online annotation of a complete bacterial genome or a small eukaryotic chromosome. The project is hosted as a Source Forge project (http://rnaspace.sourceforge.net/).

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Exceptional structured noncoding RNAs revealed by bacterial metagenome analysis

Cited by 106 publications

References 61 publications

Multiple conformations are a conserved and regulatory feature of the RB1 5′ UTR

Multiple conformations are a conserved and regulatory feature of the RB1 5′ UTR

Dual RNA-seq of pathogen and host

RNAspace.org: An integrated environment for the prediction, annotation, and analysis of ncRNA

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