A Novel Mechanism for Transcription Termination in the mod Locus of Drosophila melanogaster

The expression of protein-coding genes in eukaryotes ends with cleavage and polyadenylation, followed by the termination of transcription. Previously, we identified a non-canonical transcription terminator (NTT) in the mod(mdg4) gene of Drosophila melanogaster that causes transcription to stop, producing an mRNA that lacks a poly(A) tail. Here, we identified a minimal functional unit of the NTT consisting of 79 nucleotides that form a specific secondary RNA structure. Transcripts generated from the NTT demonstrated reduced stability and were impeded in their export to the cytoplasm. Notably, the NTT did not exhibit functionality in human cells, indicating that this termination mechanism is not universal and necessitates interaction with specific proteins. Interestingly, an NTT from the distantly related species D. willistoni could effectively terminate transcription in D. melanogaster cells, highlighting the importance of conserved motifs for NTT functionality. Overall, these findings provide insights into alternative mechanisms of transcription termination and underscore the significance of RNA primary sequences and secondary structures in potential interactions with specific proteins.