Functional genomics identifies a requirement of pre-mRNA splicing factors for sister chromatid cohesion
| Autor: | Michael Howell, Sriramkumar Sundaramoorthy, María Dolores Vázquez-Novelle, Mark Petronczki, Sergey Lekomtsev |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
RNA Splicing Factors
Spliceosome Cohesin complex RNA Splicing Nuclear Receptor Coactivators cohesin Sister chromatid exchange Cell Cycle Proteins Biology Chromatids General Biochemistry Genetics and Molecular Biology splicing RNA Precursors Humans chromosome RNA Neoplasm Molecular Biology Adaptor Proteins Signal Transducing Genetics mitosis General Immunology and Microbiology Cohesin General Neuroscience Articles Ribonucleoprotein U2 Small Nuclear Phosphoproteins Leukemia Lymphocytic Chronic B-Cell Neoplasm Proteins Establishment of sister chromatid cohesion cohesion Cytoskeletal Proteins RNA splicing Mutation Chromatid biological phenomena cell phenomena and immunity Sister Chromatid Exchange |
| Zdroj: | The EMBO Journal |
| ISSN: | 1460-2075 0261-4189 |
| Popis: | Sister chromatid cohesion mediated by the cohesin complex is essential for chromosome segregation during cell division. Using functional genomic screening, we identify a set of 26 pre-mRNA splicing factors that are required for sister chromatid cohesion in human cells. Loss of spliceosome subunits increases the dissociation rate of cohesin from chromatin and abrogates cohesion after DNA replication, ultimately causing mitotic catastrophe. Depletion of splicing factors causes defective processing of the pre-mRNA encoding sororin, a factor required for the stable association of cohesin with chromatin, and an associated reduction of sororin protein level. Expression of an intronless version of sororin and depletion of the cohesin release protein WAPL suppress the cohesion defect in cells lacking splicing factors. We propose that spliceosome components contribute to sister chromatid cohesion and mitotic chromosome segregation through splicing of sororin pre-mRNA. Our results highlight the loss of cohesion as an early cellular consequence of compromised splicing. This may have clinical implications because SF3B1, a splicing factor that we identify to be essential for cohesion, is recurrently mutated in chronic lymphocytic leukaemia. |
| Databáze: | OpenAIRE |
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