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

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 (mA) modification has recently been identified as having an important role in regulating the function of lncRNAs. However, how mA modification regulates lncRNAs following PQ exposure remains largely unknown. Herein, this study reported mA modification of lncRNAs in mouse neuroblastoma cells (Neuro-2a) following PQ induced reactive oxide species (ROS). MA sequencing was performed to explore the mA 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 mA methyltransferase and demethylase proteins, which leading to the alteration of mA modification of lncRNAs. Furthermore, the functional analysis further revealed that N-acetyl-L-cysteine (NAC)，a ROS scavengers, partly reversed PQ-induced distinct mA modificated pattern of lncRNAs. In addition, tow specific mA 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 mA modification mechanism in the field of environmental toxicology.