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| Status |
Public on Feb 04, 2022 |
| Title |
Regulation of alternative splicing by a novel BRR2 interactor C9ORF78 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The RNA helicase BRR2 (SNRNP200) is one of the key remodeling factors of the spliceosome. Here we show its direct interaction with C9ORF78, a poorly characterized protein predicted to be largely intrinsically disordered. We present cryo-EM structures showing how C9ORF78 and the spliceosomal B-complex protein FBP21 wrap around the C-terminal helicase cassette of BRR2 and that binding of the two proteins is mutually exclusive. C9ORF78 associates with the spliceosome, as we confirm via proteomics and RNA UV-crosslinking. An siRNA mediated C9ORF78 knockdown reveals changes in alternative splicing of specific target pre-mRNAs, which in part depend on its interaction with BRR2. In particular, C9ORF78 regulates a substantial number of alternative 3’ splice sites, which might be facilitated through an additional interaction with human PRP22 (DHX8).
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| Overall design |
Identification of C9orf78 RNA targets with FLASH, using GFP as a negative control
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| |
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| Contributor(s) |
Ilik I, Bergfort A, Preußner M |
| Citation(s) |
35241646 |
| |
| Submission date |
Jun 09, 2021 |
| Last update date |
Mar 30, 2022 |
| Contact name |
IBRAHIM AVSAR ILIK |
| E-mail(s) |
ilik@molgen.mpg.de
|
| Organization name |
Max-Planck-Institut für molekulare Genetik
|
| Lab |
OWL Aktas
|
| Street address |
Ihnestraße 63-73
|
| City |
Berlin |
| State/province |
Berlin |
| ZIP/Postal code |
14195 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (4)
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| Relations |
| BioProject |
PRJNA736337 |
| SRA |
SRP323369 |
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