Analysis Of MicroRNA Editing Associated With Parkinson’s Disease Based On Small RNA Sequencing

Parkinson’s disease(PD)is a common neurological degenerative disease.The main pathological change of PD is the degeneration of dopamine(DA)neurons in the midbrain substantia nigra,which results in DA content reducing and causes disease in the striatum.However,at this stage,the specific pathogenic mechanism of PD is still unclear.Micro RNA(mi RNA)is an endogenous non-coding RNA with a length of about 22 nucleotides.It is widely edited in the human brain.However,the relevant function of the mi RNA editing clusters in PD is largely unknown.Using Mi RME algorithm independently developed in our laboratory,we analyzed small RNA sequencing profiles of brain tissues in 43 patients with PD and 88 normal controls for three rounds of sequence alignments,which greatly reduced the predicted false positive rate.We identified a total of 2456 significant editing and/or mutating sites in different brain tissues of human,of which 421 loci have significantly different editing levels in PD samples.Our results indicated that two A-to-I editing sites on hsa-mi R-376 a are involved in the inhibition of urate synthase phosphate ribose pyrophosphate synthase 1(PRPS1)simultaneously.In patients with PD,the editing levels of these two editing sites changed significantly in the prefrontal cortex,which subsequently and possibly resulted in increased uric acid levels through PRPS1.These results provided new insights into understanding mi RNA editing events and their functional relevant in PD.These results provided new insights into the mechanism of PD,as well as new clues for the diagnosis and treatment of PD.