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| Status |
Public on Apr 01, 2020 |
| Title |
Defective minor spliceosomes induce SMA-associated phenotypes through sensitive intron-containing neural genes in Drosophila |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Detecting RNA levels in SMN mutation and two minor snRNAs mutation in Larva L3.
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| Contributor(s) |
Li L, Xu Y |
| Citation(s) |
33154379 |
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| Submission date |
Sep 30, 2019 |
| Last update date |
Nov 10, 2020 |
| Contact name |
Liang Li |
| E-mail(s) |
liliang@sibs.ac.cn
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| Organization name |
University of Chinese Academy of Sciences
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| Street address |
300 Fenglin Road
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| City |
Shanghai |
| ZIP/Postal code |
200032 |
| Country |
China |
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| Platforms (1) |
| GPL13304 |
Illumina HiSeq 2000 (Drosophila melanogaster) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA575006 |
| SRA |
SRP223738 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE138183_RAW.tar |
2.6 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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