Abstract
Heme oxygenase-1 (HO-1) is an inducible rate-controlling enzyme of heme catabolism. The cytoprotective function of HO-1 activity has been verified in multiple studies, and together with its by-products is considered a key component of the cellular stress response. The transcriptional induction of HO-1 has been largely studied in response to multiple forms of stressful stimuli but our understanding of HO-1 post-transcriptional control mechanisms in neuronal cells is currently lacking. In the present report we show the involvement of the RNA-binding proteins (RBPs) embryonic lethal abnormal vision (ELAV) in the regulation of HO-1 gene expression. Our study demonstrates a specific binding between HO-1 messenger RNA (mRNA) and ELAV proteins, accompanied by an increased expression of HO-1 at protein level, in a human neuroblastoma cell line treated with hemin. Clarifying the induction of HO-1 expression at post-transcriptional level may open therapeutic perspectives for treatments associated with the modulation of HO-1 expression.
Highlights
Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the initial and rate-limiting step in the oxidative degradation of heme, and generates biliverdin, free iron (Fe2+), and carbon monoxide (CO; Calabrese et al, 2006)
ASSOCIATION OF HO-1 messenger RNA (mRNA) WITH embryonic lethal abnormal vision (ELAV) RNA-binding proteins (RBPs) To test the hypothesis that ELAV RBPs interact with HO-1 mRNA following hemin treatment, we performed an immunoprecipitation assay on SH-SY5Y cells, which express all the four isoforms of ELAV proteins, followed by real-time QUANTITATIVE POLYMERASE CHAIN REACTION (qPCR)
It was recently demonstrated that RBPs and non-coding RNAs are critical components underlying the post-transcriptional mechanisms for the coordinate regulation of mRNA expression in neuronal systems (Loya et al, 2010)
Summary
Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the initial and rate-limiting step in the oxidative degradation of heme, and generates biliverdin, free iron (Fe2+), and carbon monoxide (CO; Calabrese et al, 2006). Recent studies have identified hundreds of RBPs previously unknown (Castello et al, 2012) and a new and fascinating idea is that neurons have their own systems for regulating RNA metabolism, processing, localization, and expression (Darnell, 2013). In this context, embryonic lethal abnormal vision (ELAV) proteins are RBPs mostly expressed in neurons and post-transcriptional regulation in neuronal cells strongly depends on the control exerted by these RBPs (Pascale et al, 2008). The ELAV (or Hu) family comprises the neuronspecific members HuB, HuC and HuD, and the ubiquitously
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