School of Biosciences, Cardiff University, Cardiff CF10 3AT, UK.
G3 (Bethesda). 2021 Jan 18;11(1). doi: 10.1093/g3journal/jkaa046.
The mRNA export pathway is responsible for the transport of mRNAs from the nucleus to the cytoplasm, and thus is essential for protein production and normal cellular functions. A partial loss of function allele of the mRNA export factor Nxt1 in Drosophila shows reduced viability and sterility. A previous study has shown that the male fertility defect is due to a defect in transcription and RNA stability, indicating the potential for this pathway to be implicated in processes beyond the known mRNA transport function. Here we investigate the reduced viability of Nxt1 partial loss of function mutants, and describe a defect in growth and maintenance of the larval muscles, leading to muscle degeneration. RNA-seq revealed reduced expression of a set of mRNAs, particularly from genes with long introns in Nxt1 mutant carcass. We detected differential expression of circRNA, and significantly fewer distinct circRNAs expressed in the mutants. Despite the widespread defects in gene expression, muscle degeneration was rescued by increased expression of the costamere component tn (abba) in muscles. This is the first report of a role for the RNA export pathway gene Nxt1 in the maintenance of muscle integrity. Our data also links the mRNA export pathway to a specific role in the expression of mRNA and circRNA from common precursor genes, in vivo.
mRNA 输出途径负责将 mRNA 从细胞核运输到细胞质，因此对于蛋白质的产生和正常的细胞功能至关重要。果蝇中 mRNA 输出因子 Nxt1 的部分功能丧失等位基因表现出活力降低和不育。先前的研究表明，雄性生育力缺陷是由于转录和 RNA 稳定性的缺陷所致，这表明该途径可能涉及到已知的 mRNA 运输功能之外的过程。在这里，我们研究了 Nxt1 部分功能丧失突变体的活力降低，并描述了幼虫肌肉生长和维持的缺陷，导致肌肉退化。RNA-seq 显示了一组 mRNAs 的表达降低，特别是在 Nxt1 突变体尸体中具有长内含子的基因。我们检测到 circRNA 的差异表达，并且在突变体中表达的 circRNA 明显较少。尽管存在广泛的基因表达缺陷，但 tn（abba）在肌肉中的高表达挽救了肌肉退化。这是 RNA 输出途径基因 Nxt1 在维持肌肉完整性中的作用的首次报道。我们的数据还将 mRNA 输出途径与体内常见前体基因的 mRNA 和 circRNA 表达的特定作用联系起来。
