Transposable element-gene chimeric transcripts in neural tissues: functional impacts on gene expression and behaviour and their regulatory control across model systems

Transposable elements (TEs), colloquially referred to as ‘jumping genes’, are repetitive mobile genetic elements capable of excising and inserting themselves throughout the genome. While historically dismissed as 'junk DNA', TEs constitute an extraordinary ~50% of the human genome. Together, TEs and other repetitive sequences represent the largest contributor to human genetic variation (1). Remarkably, approximately 4% of human genes incorporate transposon sequences as novel exons, and 75% of human lncRNAs contain segments of transposon origin (2). The impact of TEs extends beyond simple genome insertion; the resulting DNA, RNA and translation products can influence gene regulation, create novel coding structures, and affect chromosome stability. TE activation is increasingly recognised as a hallmark of neurodegenerative and psychiatric disorders, including Alzheimer’s disease, ALS, and schizophrenia (3). However, the molecular mechanisms governing TE-mediated variation in neural tissue remain poorly understood. This project aims to investigate how TE-gene chimeric transcripts in neural genes influence gene expression and behaviour. Using complementary model systems—Drosophila melanogaster and the parasitic nematode Strongyloides ratti—this research will characterise TE-derived chimeric mRNAs that form when intronic TEs introduce cryptic splice sites into neural genes. The comparative approach leverages distinct silencing mechanisms to identify universal and system-specific regulatory principles.