Genetic screen identifies a requirement for SMN in mRNA localisation within the Drosophila oocyte

Objective: Spinal muscular atrophy (SMA) results from insufcient levels of the survival motor neuron (SMN) protein. Drosophila is conducive to large-scale genetic-modifer screens which can reveal novel pathways underpinning the disease mechanism. We tested the ability of a large collection of genomic deletions to enhance SMN-dependent lethality. To test our design, we asked whether our study can identify loci containing genes identifed in previous genetic screens. Our objective was to fnd a common link between genes fagged in independent screens, which would allow us to expose novel functions for SMN in vivo. Results: Out of 128 chromosome defciency lines, 12 (9.4%) were found to consistently depress adult viability when crossed to SMN loss-of-function heterozygotes. In their majority, the enhancing deletions harboured genes that were previously identifed as genetic modifers, hence, validating the design of the screen. Importantly, gene overlap allowed us to fag genes with a role in post-transcriptional regulation of mRNAs that are crucial for determining the axes of the oocyte and future embryo. We fnd that SMN is also required for the correct localisation of gurken and oskar mRNAs in oocytes. These fndings extend the role of SMN in oogenesis by identifying a key requirement for mRNA trafcking.peer-reviewe