Characterisation of the function of a lncRNA containing SINE-VNTR-Alu 67 to regulate the genes at the MAPT locus

Parkinson's disease (PD) is a complex neurodegenerative disease that involves many interlinking pathways and genetic elements that remain to be fully understood and characterised. Non-coding genetic elements have long been overlooked, however recent advancements in the field have highlighted their importance with an area of interest being transposable elements. SINE-VNTR-Alu (SVA) elements are the youngest and smallest subset of retrotransposons that are only found within hominid species. SVAs have been shown to have strong regulatory impacts within our genome and can affect progression of neurodegenerative disease such as PD. Previous studies identified an SVA, polymorphic for its presence/absence, that was associated with changes in gene expression at the <i>MAPT</i> locus. This particular SVA is located within a long non-coding RNA (lncRNA) and is known as SVA_67. Here, we evaluated the SVA67-lncRNA effects on gene expression within the <i>MAPT</i> locus, a region associated with several neurodegenerative diseases in the SH-SY5Y cell line. The expression of SVA67-lncRNA in the SH-SY5Y cell line was associated with differential expression of several genes at the <i>MAPT</i> locus including <i>MAPT</i>, <i>KANSL1</i>, <i>ARL17A/B</i>, <i>LRRC37A/2</i>, and <i>NSF</i>. This study provides the first analysis of this SVA67-lncRNA and potential evidence for its involvement in complex diseases, such as PD.