Environmental influences on RNA processing: Biochemical, molecular and genetic regulators of cellular response

Pai, Athma A.; Luca, Francesca

doi:10.1002/wrna.1503

Cited by 37 publications

(27 citation statements)

References 144 publications

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“…Steady-state RNA levels are the ultimate result of synthesis rate, RNA processing and RNA stability. Both RNA processing and stability are highly regulated in every cell type (Schoenberg and Maquat 2012; Pai and Luca 2019; Yamada and Akimitsu 2019). Therefore, RNA-seq alone is insufficient to infer the accurate transcriptional activity of any given gene.…”

Section: Introductionmentioning

confidence: 99%

Rapid and scalable profiling of nascent RNA with fastGRO

Barbieri

Hill

Quesnel-Vallières

et al. 2020

Preprint

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Genome-wide profiling of nascent RNA has become a fundamental tool to study transcription regulation. Over the past decade, next-generation sequencing has fostered development of a handful of techniques (i.e. GRO-seq, PRO-seq, TT-seq and NET-seq) that map unprocessed transcripts originating from both the coding and the noncoding portion of the genome. Unlike steady-state RNA sequencing, nascent RNA profiling mirrors the real-time activity of RNA Polymerases and provides an accurate readout of transcriptome-wide variations that occur during short time frames (i.e. response to external stimuli or rapid metabolic changes). Some species of nuclear RNAs, albeit functional, have a short half-life and can only be accurately gauged by nascent RNA techniques (i.e. lincRNAs and eRNAs). Furthermore, these techniques capture uncapped post-cleavage RNA at termination sites or promoter-associated antisense RNAs, providing a unique insight into RNAPII dynamics and processivity.Here we present a run-on assay with 4s-UTP labelling, followed by reversible biotinylation and affinity purification via streptavidin. Our protocol allows streamlined sample preparation within less than 3 days. We named the technique fastGRO (fast Global Run-On). We show that fastGRO is highly reproducible and yields a more complete and extensive coverage of nascent RNA than comparable techniques. Importantly, we demonstrate that fastGRO is scalable and can be performed with as few as 0.5x10^6 cells.

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Section: Introductionmentioning

confidence: 99%

Rapid and scalable profiling of nascent RNA with fastGRO

Barbieri

Hill

Quesnel-Vallières

et al. 2020

Preprint

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“…Our observations that the splicing of cellular genes can be altered by rotavirus infection are thus consistent with alteration of the nuclear functioning by PABPC1 localization in the nucleus. Relocalization of PABPC into the nucleus have been observed in stressed cells after heat shock (56) or UV irradiation (54), and in both cases extensive changes in RNA splicing have been observed (57). Several other viral infections induce PABPC relocalization (58)(59)(60).…”

Section: Discussionmentioning

confidence: 99%

Rotavirus Infection Alters Splicing of the Stress-Related Transcription Factor XBP1

Duarte

Vende

Charpilienne

et al. 2019

J Virol

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XBP1 is a stress-regulated transcription factor also involved in mammalian host defenses and innate immune response. Our investigation of XBP1 RNA splicing during rotavirus infection revealed that an additional XBP1 RNA (XBP1es) that corresponded to exon skipping in the XBP1 pre-RNA is induced depending on the rotavirus strain used. We show that the translation product of XBP1es (XBP1es) has trans-activation properties similar to those of XBP1 on ER stress response element (ERSE) containing promoters. Using monoreassortant between ES+ (“skipping”) and ES– (“nonskipping”) strains of rotavirus, we show that gene 7 encoding the viral translation enhancer NSP3 is involved in this phenomenon and that exon skipping parallels the nuclear relocalization of cytoplasmic PABP. We further show, using recombinant rotaviruses carrying chimeric gene 7, that the ES+ phenotype is linked to the eIF4G-binding domain of NSP3. Because the XBP1 transcription factor is involved in stress and immunological responses, our results suggest an alternative way to activate XBP1 upon viral infection or nuclear localization of PABP. IMPORTANCE Rotavirus is one of the most important pathogens causing severe gastroenteritis in young children worldwide. Here we show that infection with several rotavirus strains induces an alternative splicing of the RNA encoding the stressed-induced transcription factor XBP1. The genetic determinant of XBP1 splicing is the viral RNA translation enhancer NSP3. Since XBP1 is involved in cellular stress and immune responses and since the XBP1 protein made from the alternatively spliced RNA is an active transcription factor, our observations raise the question of whether alternative splicing is a cellular response to rotavirus infection.

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“…Within a 48 hour window after acute exposure we did not observe any synergistic or Alternative splicing is a mechanism by which the exons are spliced in different ways to generate multiple transcripts from one mRNA precursor. This process contributes to protein diversity by generating different types of proteins and has been recognised as a rapid cellular mechanism in response to environmental perturbation 27 . From our experience with Drosophila, alternative splicing differences are most pronounced 24 hours after xenobiotic exposure 30 ;; for this reason we chose this time point to investigate RNA splicing in honeybees.…”

Section: Discussionmentioning

confidence: 99%

Acute Thiamethoxam exposure in Apis mellifera : Absence of both stress-induced changes in mRNA splicing and synergistic effects of common fungicide and herbicide

Décio

Ustaoglu

et al. 2019

Preprint

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Running title: Neonicotinoid toxicity is not enhanced by common fungicide and herbicide ABSTRACT Securing food supply for a growing population is a major challenge and heavily relies on the use of agrochemicals to maximize crop yield. Neonicotinoids are globally one of the most widely used insecticides. It is increasingly recognized, that some neonicotinoids have a negative impact on non-target organisms, including important pollinators such as the European honeybee Apis mellifera. Toxicity of neonicotinoids may be enhanced through simultaneous exposure with additional pesticides, which could help explain, in part, the global decline of honeybee colonies. Here we examined whether exposure effects of the neonicotinoid Thiamethoxam are enhanced by the commonly used fungicide Carbendazim and the herbicide Glyphosate. We also analysed alternative splicing changes upon pesticide exposure in the honeybee. In particular, we examined transcripts of three genes: i) the stress sensor gene X box binding protein-1 (Xbp1), ii) the Down Syndrome Cell Adhesion Molecule (Dscam) gene and iii) the embryonic lethal/abnormal visual system (elav) gene, which are important for neuronal function. Our results showed that acute neonicotinoid exposure is not enhanced by Carbendazim, nor Glyphosate. Toxicity of the compounds did not trigger stress-induced, alternative splicing in the analysed mRNAs, thereby leaving dormant a cellular response pathway to these man-made environmental perturbations.

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Environmental influences on RNA processing: Biochemical, molecular and genetic regulators of cellular response

Cited by 37 publications

References 144 publications

Rapid and scalable profiling of nascent RNA with fastGRO

Rapid and scalable profiling of nascent RNA with fastGRO

Rotavirus Infection Alters Splicing of the Stress-Related Transcription Factor XBP1

Acute Thiamethoxam exposure in Apis mellifera : Absence of both stress-induced changes in mRNA splicing and synergistic effects of common fungicide and herbicide

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