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Series GSE145872 Query DataSets for GSE145872
Status Public on Apr 06, 2020
Title The CWC27/CWC22 heterodimer: a spliceosome building block linked to the inflammation response in retinal pigment epithelium
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Human CWC27 is an uncharacterized splicing factor and mutations in its gene are linked to retinal degeneration and other developmental defects. We identify the splicing factor CWC22 as the major CWC27 partner. Both CWC27 and CWC22 are present in published Bact spliceosome structures, but no interacting domains are visible. Here, the structure of a CWC27/CWC22 heterodimer bound to the Exon Junction Complex (EJC) core component eIF4A3 is solved at 3Å-resolution. According to spliceosomal structures, the EJC is recruited in the C complex, once CWC27 has left. Our 3D structure of the eIF4A3/CWC22/CWC27 complex is compatible with the Bact spliceosome structure but not with that of the C complex, where a CWC27 loop would clash with the EJC core subunit Y14. A CWC27/CWC22 building block might thus form an intermediate landing platform for eIF4A3 onto the Bact complex prior to its conversion into C complex. Knock-down of either CWC27 or CWC22 in immortalized retinal pigment epithelial cells affects numerous common genes, indicating that these proteins cooperate, targeting the same pathways. As the most up-regulated genes encode factors involved in inflammation, our findings suggest a possible link to the retinal degeneration associated with CWC27 deficiencies.
Overall design 9 RNA-seq samples were analyzed. 3 controls samples, 3 samples with siRNA depletion of CWC22 and 3 samples with siRNA depletion of CWC27.
Contributor(s) Busetto V, Barbosa I, Basquin J, Marquenet É, Hocq R, Hennion M, Paternina JA, Namane A, Conti E, Bensaude O, Le Hir H
Citation(s) 32329775
Submission date Feb 24, 2020
Last update date Apr 27, 2020
Contact name Herve Le Hir
Organization name IBENS
Lab ENS, CNRS, INSERM, PSL Research University
Street address 46, Rue d’Ulm
City Paris
ZIP/Postal code 75005
Country France
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (9)
GSM4338280 Ctrl-1
GSM4338281 Ctrl-2
GSM4338282 Ctrl-3
BioProject PRJNA608562
SRA SRP250614

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE145872_CWC22-deseq2.tabular.txt.gz 1.4 Mb (ftp)(http) TXT
GSE145872_RAW.tar 3.1 Mb (http)(custom) TAR (of TAB)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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