Investigation of Chimeric Transcripts Derived from LINE-1 and Alu Retrotransposons in Cerebellar Tissues of Individuals with Autism Spectrum Disorder (ASD)

LINE-1 and Alu retrotransposons are components of the human genome and have been implicated in many human diseases. These elements can influence human transcriptome plasticity in various mechanisms. Chimeric transcripts derived from LINE-1 and Alu can also impact the human transcriptome, such as exonization and post-transcriptional modification. However, its specific role in ASD neuropathology remains unclear, particularly in the cerebellum tissues. We performed RNA-sequencing of post-mortem cerebellum tissues from ASD and unaffected individuals for transposable elements profiling and chimeric transcript identification. The majority of free transcripts of transposable elements were not changed in the cerebellum tissues of ASD compared with unaffected individuals. Nevertheless, we observed that chimeric transcripts derived from LINE-1 and Alu were embedded in the transcripts of differentially expressed genes in the cerebellum of ASD, and these genes were related to developments and abnormalities of the cerebellum. In addition, the expression levels of these genes were correlated with the significantly decreased thickness of the molecular layer in the cerebellum of ASD. We also found that global methylation and expression of LINE-1 and Alu elements were not changed in ASD, but observed in the ASD sub-phenotypes. Our findings showed associations between transposable elements and cerebellar abnormalities in ASD, particularly in distinct phenotypic subgroups. Further investigations using appropriate models are warranted to elucidate the structural and functional implications of LINE-1 and Alu elements in ASD neuropathology. Post-mortem cerebellum tissues from ASD and unaffected individuals were originally obtained from the Harvard Brain Tissue Resource Center. The snap-frozen post-mortem brain tissues used in this study consist of 13 samples from cerebellum tissues of ASD (n=8) and unaffected controls (n=5). The snap-frozen post-mortem brain tissues were used for RNA isolations before molecular analysis. Total RNA was sent to BGI Hong Kong for RNA-sequencing analysis using the MGI DNBSEQ technology platform. Briefly, total RNA was used to prepare stranded mRNA library construction by mRNA enrichment and was then sequenced by the DNBSEQ-G400 (150 bp paired-end).