Functional characterisation of the survival motor neuron complex member Gemin5

Abstract

Spinal Muscular Atrophy (SMA) is a neurodegenerative disease characterized by loss of motor neurons as a result of a deficiency of the survival of motor neuron (SMN) gene. The SMN gene encodes a protein, the SMN protein, which exists in the cell as part of a large complex where it associates with at least 9 other proteins, which together play a role in the assembly of different classes of ribonucleoproteins (RNPs) in RNA processing. The SMN gene is highly conserved in evolution and is detected in various animals, leading to the development of animal models to model human diseases like SMA, in an attempt to understand its pathogenesis in humans. Due to its rapid generation time and the vast choice of genetic tools which can be used, the fruit fly, Drosophila melanogaster, has been widely used to model SMA amongst other neurodegenerative diseases, for the correct interpretation of the phenotypes produced as a result of such disease. In this study, Drosophila was used for the functional assessment of Gemin5, one of the peripheral components of the SMN complex. A role in larval development as well as in RNP processing has been observed in the ortholog of human Gemin5, termed Rigor Mortis (Rig). Further functional assessment of Gemin5 in Drosophila was carried out by observing phenotypes produced by Gemin5 specific loss-of-function mutants as well as Gemin5 knockdown via larval mobility assays and adult viability assays respectively. Results demonstrated that that total removal of gemin5 brings about lethality at an early stage of development, suggesting that Gemin5 activity is essential for regular development of flies. It was also concluded, that Gemin5 is required in large quantities for appropriate muscle operation. Such findings compliment a possible function of Gemi Clearly, additional studies should provide insights into the significance of Gemin5 and its functions, as well as its contribution within the SMN complex, with the hope of clarifying the molecular mechanisms underlying SMA.