Role of miRNAs and alternative mRNA 3′-end cleavage and polyadenylation of their mRNA targets in cardiomyocyte hypertrophy

Soetanto, Rina; Hynes, Carly J.; Patel, Hardip R.; Humphreys, David T.; Evers, M.; Duan, Guowen; Parker, Brian J.; Archer, Stuart K.; Clancy, Jennifer L.; Graham, Robert M.; Beilharz, Traude H.; Smith, Nicola J.; Preiß, Thomas

doi:10.1016/j.bbagrm.2016.03.010

Cited by 19 publications

(19 citation statements)

References 55 publications

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“…To identify transcripts enriched in oxidation resulting from oxidative stress associated with the formaldehyde exposure, candidate transcripts (p adj < 0.05) resulting from the DESeq2 analysis between immunoprecipitated and input RNA pools were filtered for further analysis. Differences in log 2 fold changes between these transcripts in the formaldehyde treatment and their corresponding transcripts in the clean air condition were calculated by subtracting the DESeq2-generated log 2 FC value of clean air controls from that of formaldehyde exposed samples for each transcript (∆log 2 FC = FA log2FC − CA log2FC ), similar to that performed by Soetanto et al 68 . Log 2 FC values of 0.00 were raised to 0.01 to enable log calculations without influencing count data.…”

Section: Discussionmentioning

confidence: 99%

RNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde

Gonzalez-Rivera

Sherman

Wang

et al. 2020

Sci Rep

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Formaldehyde is an environmental and occupational chemical carcinogen implicated in the damage of proteins and nucleic acids. However, whether formaldehyde provokes modifications of RNAs such as 8-oxo-7,8-dihydroguanine (8-oxoG) and the role that these modifications play on conferring long-term adverse health effects remains unexplored. Here, we profile 8-oxoG modifications using RNA-immunoprecipitation and RNA sequencing (8-oxoG RIP-seq) to identify 343 RNA transcripts heavily enriched in oxidations in human bronchial epithelial BEAS-2B cell cultures exposed to 1 ppm formaldehyde for 2 h. RNA oxidation altered expression of many transcripts involved in chromatin modification and p53-mediated DNA-damage responses, two pathways that play key roles in sustaining genome integrity and typically deregulated in tumorigenesis. Given that these observations were identified in normal cells exhibiting minimal cell stress and death phenotypes (for example, lack of nuclear shrinkage, F-actin alterations or increased LDH activity); we hypothesize that oxidative modification of specific RNA transcripts following formaldehyde exposure denotes an early process occurring in carcinogenesis analogous to the oxidative events surfacing at early stages of neurodegenerative diseases. As such, we provide initial investigations of RNA oxidation as a potentially novel mechanism underlying formaldehyde-induced tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

RNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde

Gonzalez-Rivera

Sherman

Wang

et al. 2020

Sci Rep

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“…In reference to the experiment shown in Additional file 1 : Figure S1, surplus tissue (left and right ventricles, left and right atria, aorta, kidney, lung, liver, and brain) from sham-operated wild-type C57BL/6J mice (12 weeks old, male), as harvested for a previous study [ 12 ], was used to generate cDNA to quantify GPR37L1 by qPCR.…”

Section: Methodsmentioning

confidence: 99%

Orphan receptor GPR37L1 contributes to the sexual dimorphism of central cardiovascular control

Coleman

Mouat

et al. 2018

Biol Sex Differ

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BackgroundOver 100 mammalian G protein-coupled receptors are yet to be matched with endogenous ligands; these so-called orphans are prospective drug targets for the treatment of disease. GPR37L1 is one such orphan, abundant in the brain and detectable as mRNA in the heart and kidney. GPR37L1 ablation was reported to cause hypertension and left ventricular hypertrophy, and thus, we sought to further define the role of GPR37L1 in blood pressure homeostasis.MethodsWe investigated the cardiovascular effects of GPR37L1 using wild-type (GPR37L1wt/wt) and null (GPR37L1KO/KO) mice established on a C57BL/6J background, both under baseline conditions and during AngII infusion. We profiled GPR37L1 tissue expression, examining the endogenous receptor by immunoblotting and a β-galactosidase reporter mouse by immunohistochemistry.ResultsGPR37L1 protein was abundant in the brain but not detectable in the heart and kidney. We measured blood pressure in GPR37L1wt/wt and GPR37L1KO/KO mice and found that deletion of GPR37L1 causes a female-specific increase in systolic, diastolic, and mean arterial pressures. When challenged with short-term AngII infusion, only male GPR37L1KO/KO mice developed exacerbated left ventricular hypertrophy and evidence of heart failure, while the female GPR37L1KO/KO mice were protected from cardiac fibrosis.ConclusionsDespite its absence in the heart and kidney, GPR37L1 regulates baseline blood pressure in female mice and is crucial for cardiovascular compensatory responses in males. The expression of GPR37L1 in the brain, yet absence from peripheral cardiovascular tissues, suggests this orphan receptor is a hitherto unknown contributor to central cardiovascular control.Electronic supplementary materialThe online version of this article (10.1186/s13293-018-0173-y) contains supplementary material, which is available to authorized users.

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“…This switch establishes a potential scenario where a shortened 3′UTR can evade miRNA-mediated gene repression and consequently increase protein expression. Over the past few years, the importance of APA has been highlighted in several pathological states, including malignancies and cardiac disorders ( Creemers et al, 2016 ; Masamha et al, 2014 ; Singh et al, 2009 ; Soetanto et al, 2016 ; Tian and Manley, 2017 ; Xia et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of CFIm25 amplifies dermal fibrosis through alternative polyadenylation

Weng

Huang

Wagner

et al. 2019

Journal of Experimental Medicine

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Systemic sclerosis (SSc; scleroderma) is a multisystem fibrotic disease. The mammalian cleavage factor I 25-kD subunit (CFIm25; encoded by NUDT21) is a key regulator of alternative polyadenylation, and its depletion causes predominantly 3′UTR shortening through loss of stimulation of distal polyadenylation sites. A shortened 3′UTR will often lack microRNA target sites, resulting in increased mRNA translation due to evasion of microRNA-mediated repression. Herein, we report that CFlm25 is downregulated in SSc skin, primary dermal fibroblasts, and two murine models of dermal fibrosis. Knockdown of CFIm25 in normal skin fibroblasts is sufficient to promote the 3′UTR shortening of key TGFβ-regulated fibrotic genes and enhance their protein expression. Moreover, several of these fibrotic transcripts show 3′UTR shortening in SSc skin. Finally, mice with CFIm25 deletion in fibroblasts show exaggerated skin fibrosis upon bleomycin treatment, and CFIm25 restoration attenuates bleomycin-induced skin fibrosis. Overall, our data link this novel RNA-processing mechanism to dermal fibrosis and SSc pathogenesis.

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Role of miRNAs and alternative mRNA 3′-end cleavage and polyadenylation of their mRNA targets in cardiomyocyte hypertrophy

Cited by 19 publications

References 55 publications

RNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde

RNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde

Orphan receptor GPR37L1 contributes to the sexual dimorphism of central cardiovascular control

Downregulation of CFIm25 amplifies dermal fibrosis through alternative polyadenylation

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