Abstract
Lead is a metal that has toxic effects on the developing nervous system. However, the mechanisms underlying lead-induced neurotoxicity are not well understood. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation, but few studies have examined the function of ncRNAs in lead-induced neurotoxicity. We addressed this in the present study by evaluating the functions of a long non-coding RNA (named lncRpa) and a circular RNA (named circRar1) in a mouse model of lead-induced neurotoxicity. High-throughput RNA sequencing showed that both lncRpa and circRar1 promoted neuronal apoptosis. We also found that lncRpa and circRar1 induced the upregulation of apoptosis-associated factors caspase8 and p38 at the mRNA and protein levels via modulation of their common target microRNA miR-671. This is the first report of a regulatory interaction among a lncRNA, circRNA, and miRNA mediating neuronal apoptosis in response to lead toxicity.
Highlights
Lead is an industrial and environmental pollutant that can cause pathological changes to multiple organ systems, including the nervous system
The present study investigated the functions of Long non-coding RNAs (lncRNAs) and circRNAs in lead-induced neurotoxicity
The total number of nucleotides in the human genome is 30 times that of the nematode genome, the number of protein-coding sequences is comparable, which highlights the importance of non-coding RNAs (ncRNAs) sequences in the regulation of eukaryotic gene expression (Costa 2008)
Summary
Lead is an industrial and environmental pollutant that can cause pathological changes to multiple organ systems, including the nervous system. There have been few studies investigating the role of non-coding RNAs (ncRNAs) in this process, they have been shown to play important roles in many biological processes, including transcriptional regulation, DNA replication, RNA processing, mRNA stability and translation, and protein degradation and transport (Storz 2002). Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have been the focus of many recent studies on ncRNA function. These molecules were originally identified in an RNA virus (Wilusz and Sharp 2013); they are widely present in mammalian cells and have been linked to the regulation of gene expression (Zhang et al 2014), alternative splicing (Lasda and Parker 2014), and translation through interaction with RNA-binding proteins (Zhang et al 2013).
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