Open AccessHuman Cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion
Author(s) -
Isabella M.Y. Zanini,
Charlotte Soneson,
Luca E. Lorenzi,
Claus M. Azzalin
Publication year - 2017
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.194068
Subject(s) - biology , establishment of sister chromatid cohesion , spliceosome , rna splicing , genetics , sister chromatids , microbiology and biotechnology , splicing factor , gene , alternative splicing , genome instability , rna , chromosome , messenger rna , dna , dna damage
Cactins constitute a family of eukaryotic proteins broadly conserved from yeast to human and required for fundamental processes such as cell proliferation, genome stability maintenance, organismal development and immune response. Cactin proteins have been found to associate with the spliceosome in several model organisms, nevertheless their molecular functions await elucidation. Here we show that depletion of human Cactin (hCactin) leads to premature sister chromatid separation, genome instability and cell proliferation arrest. Moreover, hCactin is essential for efficient splicing of thousands of pre-mRNAs, and incomplete splicing of the pre-mRNA of Sororin, a cohesin-associated factor, is largely responsible for the aberrant chromatid separation in hCactin-depleted cells. Lastly, hCactin physically and functionally interacts with the spliceosome-associated factors DHX8 and SRRM2. We propose that cellular complexes comprising hCactin, DHX8 and SRRM2 sustain precise chromosome segregation, genome stability and cell proliferation by allowing faithful splicing of specific pre-mRNAs. Our data point to novel pathways of gene expression regulation dependent on hCactin, and provide an explanation for the pleiotropic dysfunctions deriving from Cactin inactivation in distant eukaryotes.