Antisense expression increases gene expression variability and locus interdependency

Xu, Zhenyu; Wei, Wu; Gagneur, Julien; Clauder‐Münster, Sandra; Smolik, M.; Huber, Wolfgang; Steinmetz, Lars M.

doi:10.1038/msb.2011.1

Cited by 170 publications

(194 citation statements)

References 35 publications

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“…In addition to biochemical diversity, a common theme for lncRNA function is temporal control of gene expression, regulating cellular programs that require highly specific and well timed responses to extracellular stimuli. [28][29][30] Unsurprisingly, misregulation of lncRNAs has been linked to the development of a multitude of human diseases including cancer 31 and heart failure. 32 The budding yeast Saccharomyces cerevisiae has been a robust system for genetic and molecular investigation of gene expression steps since its introduction as a model organism almost 30 y ago.…”

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confidence: 99%

“…104 Repression DCI1 Fatty acid metabolism YES GAL10 lncRNA 47,48,105 Repression GAL genes Galactose metabolism YES GAL10/GAL10s lncRNAs. 52,53 Promotes induction GAL genes Galactose metabolism YES KCS1 lncRNAs 106 Translational interference KCS1 Inositol hexa/hepta bisphosphate kinase YES SUT719 30,35 Repression SUR7 Plasma membrane protein YES CDC28 AS RNA 29 Promotes induction CDC28 Cell cycle regulator NO RTL. 107 Repression Ty1 Retrotransposon NO ICR1.…”

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confidence: 99%

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LncRNAs: Bridging environmental sensing and gene expression

2016

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The survival of all organisms is dependent on complex, coordinated responses to environmental cues. Non-coding RNAs have been identified as major players in regulation of gene expression, with recent evidence supporting roles for long non-coding (lnc)RNAs in both transcriptional and post-transcriptional control. Evidence from our laboratory shows that lncRNAs have the ability to form hybridized structures called R-loops with specific DNA target sequences in S. cerevisiae, thereby modulating gene expression. In this Point of View, we provide an overview of the nature of lncRNA-mediated control of gene expression in the context of our studies using the GAL gene cluster as a model for controlling the timing of transcription.

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confidence: 99%

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confidence: 99%

LncRNAs: Bridging environmental sensing and gene expression

2016

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“…Furthermore, lncRNAs are known to regulate expression of both proximal (cis) and distal (trans) protein-coding genes (Kornienko et al, 2013). In particular, antisense lncRNAs are involved in transcription regulation of protein-coding genes in cis (Wilusz et al, 2009;Xu et al, 2011). Our results suggest potential regulatory roles of the antisense lncRNA NONHSAG011351 on ERBB3 in human islets.…”

Section: Discussionmentioning

confidence: 72%

The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus

Kaur

Mirza

Brorsson

et al. 2016

Molecular and Cellular Endocrinology

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a b s t r a c tThe study aimed to explore the role of ERBB3 in type 1 diabetes (T1D). We examined whether genetic variation of ERBB3 (rs2292239) affects residual b-cell function in T1D cases. Furthermore, we examined the expression of ERBB3 in human islets, the effect of ERBB3 knockdown on apoptosis in insulinproducing INS-1E cells and the genetic and regulatory architecture of the ERBB3 locus to provide insights to how rs2292239 may confer disease susceptibility. rs2292239 strongly correlated with residual b-cell function and metabolic control in children with T1D. ERBB3 locus associated lncRNA (NON-HSAG011351) was found to be expressed in human islets. ERBB3 was expressed and down-regulated by pro-inflammatory cytokines in human islets and INS-1E cells; knockdown of ERBB3 in INS-1E cells decreased basal and cytokine-induced apoptosis. Our data suggests an important functional role of ERBB3 and its potential regulators in the b-cells and may constitute novel targets to prevent b-cell destruction in T1D.

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“…Indeed, using available genome-wide measurements of noise obtained by Newman et al 23 and plasticity by Tirosh and Barkai, 24 we have found that the level of antisense transcription across a gene is well correlated with both features (unpublished data). In support of this, Xu et al 25 also showed that genes with defined overlapping antisense transcripts showed a higher variation of gene expression across 5 different environmental conditions compared to those genes that did not. Another possibility is that antisense transcription might enforce the stochastic, 'burstier' mode of sense transcription that is characterized by infrequent, rapid bouts of transcription initiation, which can be observed as bright dots using RNA-FISH, and which is known to be inherently noisy.…”

Section: Roles For Dynamic Chromatinmentioning

confidence: 86%

Using both strands: The fundamental nature of antisense transcription

Murray¹,

Mellor

2016

BioArchitecture

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ABSTRACT. Non-coding transcription across the antisense strands of genes is an abundant, pervasive process in eukaryotes from yeast to humans, however its biological function remains elusive. Here, we provide commentary on a recent study of ours, which demonstrates a genome-wide role for antisense transcription: establishing a unique, dynamic chromatin architecture over genes. Antisense transcription increases the level of nucleosome occupancy and histone acetylation at the promoter and body of genes, without necessarily modulating the level of protein-coding sense transcription. It is also associated with high levels of histone turnover. By allowing genes to sample a wider range of chromatin configurations, antisense transcription could serve to make genes more sensitive to changing signals, priming them for responses to developmental programs or stressful cellular environments. Given the abundance of antisense transcription and the breadth of these chromatin changes, we propose that antisense transcription represents a fundamental, canonical feature of eukaryotic genes.

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Antisense expression increases gene expression variability and locus interdependency

Abstract: The function of non-coding antisense RNAs in yeast remains to be fully understood. Steinmetz and colleagues provide evidence for a general regulatory effect of antisense expression on sense genes and for a role in spreading regulatory signals between neighboring genes.

Cited by 170 publications

References 35 publications

LncRNAs: Bridging environmental sensing and gene expression

LncRNAs: Bridging environmental sensing and gene expression

The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus

Using both strands: The fundamental nature of antisense transcription

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