title: Human cactin interacts with DHX8 and SRRM2 to assure efficient pre-mRNA splicing and sister chromatid cohesion.
abstract: 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 leads to premature sister chromatid separation, genome instability and cell proliferation arrest. Moreover, cactin is essential for efficient splicing of thousands of pre-mRNAs, and incomplete splicing of the pre-mRNA of sororin (also known as CDCA5), a cohesin-associated factor, is largely responsible for the aberrant chromatid separation in cactin-depleted cells. Lastly, cactin physically and functionally interacts with the spliceosome-associated factors DHX8 and SRRM2. We propose that cellular complexes comprising cactin, 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 cactin, and provide an explanation for the pleiotropic dysfunctions deriving from cactin inactivation in distant eukaryotes.
authors.affiliation: Institute of Biochemistry (IBC), Department of Biology, Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich CH-8093, Switzerland.
authors.forename: Isabella M Y
authors.initials: IM
authors.lastname: Zanini
authors.affiliation: Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne CH-1015, Switzerland.
authors.forename: Charlotte
authors.identifier: 0000-0003-3833-2169
authors.initials: C
authors.lastname: Soneson
authors.affiliation: Institute of Biochemistry (IBC), Department of Biology, Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich CH-8093, Switzerland.
authors.forename: Luca E
authors.initials: LE
authors.lastname: Lorenzi
authors.affiliation: Institute of Biochemistry (IBC), Department of Biology, Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich CH-8093, Switzerland claus.azzalin@bc.biol.ethz.ch.
authors.forename: Claus M
authors.identifier: 0000-0002-9396-1980
authors.initials: CM
authors.lastname: Azzalin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D053144:Cell Nucleus Shape; D049109:Cell Proliferation; D002842:Chromatids / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D042822:Genomic Instability; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D011485:Protein Binding; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics*; D000072260:RNA Splicing Factors / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C500695:CDCA5 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D012322:RNA Precursors; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C414618:SRRM2 protein, human; C000621740:cactin protein, human; D053487:DEAD-box RNA Helicases; C545297:DHX8 protein, human
keywords: Cactin; DHX8; Pre-mRNA splicing; SRRM2; Sister chromatid cohesion; Sororin