Paraquat-induced oxidative stress regulates N6-methyladenosine (m6A) modification of long noncoding RNAs in Neuro-2a cells

Abstract

Paraquat (PQ) is a ubiquitously applied herbicide. Long-term PQ exposure with low dose has been reported to induce abnormal expression of long non-coding RNAs (lncRNAs) in brain nerve cells, which could further lead to Parkinson's disease (PD). N6-methyladenosine (m⁶A) modification has recently been identified as having an important role in regulating the function of lncRNAs. However, how m⁶A modification regulates lncRNAs following PQ exposure remains largely unknown. Herein, this study reported m⁶A modification of lncRNAs in mouse neuroblastoma cells (Neuro-2a) following PQ induced reactive oxide species (ROS). M⁶A sequencing was performed to explore the m⁶A modificated pattern of lncRNAs in Neuro-2a cells which were treated with 200 μM PQ for 3 h. It was found that PQ hypermethylated total RNA and changed the expression of m⁶A methyltransferase and demethylase proteins, which leading to the alteration of m⁶A modification of lncRNAs. Furthermore, the functional analysis further revealed that N-acetyl-L-cysteine (NAC)，a ROS scavengers, partly reversed PQ-induced distinct m⁶A modificated pattern of lncRNAs. In addition, tow specific m⁶A modified lncRNAs were identified: cell division cycle 5-like (lncRNA CDC5L) and signal transducer and activator of transcription 3 (lncRNA STAT3), which could influence downstream autophagy related biological function. In summary, this work could potentially contribute to the new insight of lncRNAs m⁶A modification mechanism in the field of environmental toxicology.