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Citation
Li, L., Ding, Z., Pang, T.L., Zhang, B., Li, C.H., Liang, A.M., Wang, Y.R., Zhou, Y., Fan, Y.J., Xu, Y.Z. (2020). Defective minor spliceosomes induce SMA-associated phenotypes through sensitive intron-containing neural genes in Drosophila.  Nat. Commun. 11(1): 5608.
FlyBase ID
FBrf0247174
Publication Type
Research paper
Abstract

The minor spliceosome is evolutionarily conserved in higher eukaryotes, but its biological significance remains poorly understood. Here, by precise CRISPR/Cas9-mediated disruption of the U12 and U6atac snRNAs, we report that a defective minor spliceosome is responsible for spinal muscular atrophy (SMA) associated phenotypes in Drosophila. Using a newly developed bioinformatic approach, we identified a large set of minor spliceosome-sensitive splicing events and demonstrate that three sensitive intron-containing neural genes, Pcyt2, Zmynd10, and Fas3, directly contribute to disease development as evidenced by the ability of their cDNAs to rescue the SMA-associated phenotypes in muscle development, neuromuscular junctions, and locomotion. Interestingly, many splice sites in sensitive introns are recognizable by both minor and major spliceosomes, suggesting a new mechanism of splicing regulation through competition between minor and major spliceosomes. These findings reveal a vital contribution of the minor spliceosome to SMA and to regulated splicing in animals.

PubMed ID
PubMed Central ID
PMC7644725 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Commun.
    Title
    Nature communications
    ISBN/ISSN
    2041-1723
    Data From Reference
    Aberrations (2)
    Alleles (28)
    Genes (89)
    Human Disease Models (1)
    Physical Interactions (24)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (20)
    Experimental Tools (4)
    Transgenic Constructs (23)