The many facets of RNA-binding protein HuR

Rajasingh, Johnson

doi:10.1016/j.tcm.2015.03.013

Cited by 13 publications

(11 citation statements)

References 19 publications

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“…Although we did not observe significant changes following 6 h irradiation at 0.05 Gy (Figure 4B), 12 h exposure to 0.05 Gy irradiation reduced the steady-state expression levels of HuR target genes, consistent with the observation that HuR KO considerably decreased the levels of HuR target mRNAs (Figure 4C). This implies that LDIR can suppress HuR activity, leading to decreased expression of HuR target genes, consistent with previous observations that HuR stabilizes its target mRNAs [23][24][25].…”

Section: Ldir Modulates the Stability Of Hur-crosslinked Mrnassupporting

confidence: 91%

Low-Dose Ionizing Radiation-Crosslinking Immunoprecipitation (LDIR-CLIP) Identified Irradiation-Sensitive RNAs for RNA-Binding Protein HuR-Mediated Decay

Lee,

Mun,

Kim

et al. 2023

Biology

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Although ionizing radiation (IR) is widely used for therapeutic and research purposes, studies on low-dose ionizing radiation (LDIR) are limited compared with those on other IR approaches, such as high-dose gamma irradiation and ultraviolet irradiation. High-dose IR affects DNA damage response and nucleotide–protein crosslinking, among other processes; however, the molecular consequences of LDIR have been poorly investigated. Here, we developed a method to profile RNA species crosslinked to an RNA-binding protein, namely, human antigen R (HuR), using LDIR and high-throughput RNA sequencing. The RNA fragments isolated via LDIR-crosslinking and immunoprecipitation sequencing were crosslinked to HuR and protected from RNase-mediated digestion. Upon crosslinking HuR to target mRNAs such as PAX6, ZFP91, NR2F6, and CAND2, the transcripts degraded rapidly in human cell lines. Additionally, PAX6 and NR2F6 downregulation mediated the beneficial effects of LDIR on cell viability. Thus, our approach provides a method for investigating post-transcriptional gene regulation using LDIR.

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Section: Ldir Modulates the Stability Of Hur-crosslinked Mrnassupporting

confidence: 91%

Low-Dose Ionizing Radiation-Crosslinking Immunoprecipitation (LDIR-CLIP) Identified Irradiation-Sensitive RNAs for RNA-Binding Protein HuR-Mediated Decay

Lee,

Mun,

Kim

et al. 2023

Biology

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“…Despite being highly expressed in the heart, relatively little is known about the role of HuR in the myocardium. However, there is growing interest in the functional role that HuR and other RNA binding proteins may play as central regulators of posttranscriptional gene expression in cardiac physiology and pathology (6,7). To assess the functional role of HuR in the development and progression of pathological cardiac hypertrophy, we created the first cardiac-specific HuR deletion mouse to our knowledge (iCM-HuR -/-).…”

Section: Discussionmentioning

confidence: 99%

“…Human antigen R (HuR; encoded by the Elavl1 gene) is an RNA binding protein that binds to AU-rich regions in the 3′-untranslated region of many different mRNAs, including many involved in inflammation, cell growth, and fibrosis, and it directly regulates the expression of target mRNA through modulation of its stability and/or translation (4,5). While relatively little is known about the role of HuR in the myocardium, RNA binding proteins such as HuR are becoming recognized as potentially central regulators of cardiac physiology and pathology (6,7). We have recently shown that HuR is both necessary and sufficient for hypertrophic growth in cultured primary rat myocytes in response to hypertrophic stimuli in vitro (8).…”

Section: Introductionmentioning

confidence: 99%

Human antigen R as a therapeutic target in pathological cardiac hypertrophy

Green¹,

Anthony²,

Slone³

et al. 2019

JCI Insight

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“…[1-4] While relatively little is known about the role of HuR in the myocardium, RNA binding proteins such as HuR are becoming recognized as potentially central regulators of cardiac physiology and pathology. [5,6] Recent work by Krishnamurthy et al suggests that HuR is likely to play a central role in the cardiac response to stress. [7,8] They showed that HuR expression increased following ischemic injury and knockdown with shRNA delivered via intra-myocardial injection significantly reduced post- infarct remodeling and was accompanied by a decrease in transforming growth factor-β (TGF-β) expression.…”

Section: Introductionmentioning

confidence: 99%

Activation of HuR downstream of p38 MAPK promotes cardiomyocyte hypertrophy

Slone

Anthony

et al. 2016

Cellular Signalling

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The RNA binding protein Human antigen R (HuR) interacts with specific AU-rich domains in target mRNAs and is highly expressed in many cell types, including cardiomyocytes. However, the role of HuR in cardiac physiology is largely unknown. Our results show that HuR undergoes cytoplasmic translocation, indicative of its activation, in hypertrophic cardiac myocytes. Specifically, HuR cytoplasmic translocation is significantly increased in NRVMs (neonatal rat ventricular myocytes) following treatment with phenylephrine or angiotensin II, agonists of two independent Gαq-coupled GPCRs known to induce hypertrophy. This Gq-mediated HuR activation is dependent on p38 MAP kinase, but not canonical Gq-PKC signaling. Furthermore, we show that HuR activation is necessary for Gq-mediated hypertrophic growth of NRVMs as siRNA-mediated knockdown of HuR inhibits hypertrophy as measured by cell size and expression of ANF (atrial natriuretic factor). Additionally, HuR overexpression is sufficient to induce hypertrophic cell growth. To decipher the downstream mechanisms by which HuR translocation promotes cardiomyocyte hypertrophy, we assessed the role of HuR in the transcriptional activity of NFAT (nuclear factor of activated T cells), the activation of which is a hallmark of cardiac hypertrophy. Using an NFAT-luciferase reporter assay, we show an acute inhibition of NFAT transcriptional activity following pharmacological inhibition of HuR. In conclusion, our results identify HuR as a novel mediator of cardiac hypertrophy downstream of the Gq-p38 MAPK pathway, and suggest modulation of NFAT activity as a potential mechanism.

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The many facets of RNA-binding protein HuR

Cited by 13 publications

References 19 publications

Low-Dose Ionizing Radiation-Crosslinking Immunoprecipitation (LDIR-CLIP) Identified Irradiation-Sensitive RNAs for RNA-Binding Protein HuR-Mediated Decay

Low-Dose Ionizing Radiation-Crosslinking Immunoprecipitation (LDIR-CLIP) Identified Irradiation-Sensitive RNAs for RNA-Binding Protein HuR-Mediated Decay

Human antigen R as a therapeutic target in pathological cardiac hypertrophy

Activation of HuR downstream of p38 MAPK promotes cardiomyocyte hypertrophy

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