title: Tudor staphylococcal nuclease is an evolutionarily conserved component of the programmed cell death degradome.
abstract: Programmed cell death (PCD) is executed by proteases, which cleave diverse proteins thus modulating their biochemical and cellular functions. Proteases of the caspase family and hundreds of caspase substrates constitute a major part of the PCD degradome in animals. Plants lack close homologues of caspases, but instead possess an ancestral family of cysteine proteases, metacaspases. Although metacaspases are essential for PCD, their natural substrates remain unknown. Here we show that metacaspase mcII-Pa cleaves a phylogenetically conserved protein, TSN (Tudor staphylococcal nuclease), during both developmental and stress-induced PCD. TSN knockdown leads to activation of ectopic cell death during reproduction, impairing plant fertility. Surprisingly, human TSN (also known as p100 or SND1), a multifunctional regulator of gene expression, is cleaved by caspase-3 during apoptosis. This cleavage impairs the ability of TSN to activate mRNA splicing, inhibits its ribonuclease activity and is important for the execution of apoptosis. Our results establish TSN as the first biological substrate of metacaspase and demonstrate that despite the divergence of plants and animals from a common ancestor about one billion years ago and their use of distinct PCD pathways, both have retained a common mechanism to compromise cell viability through the cleavage of the same substrate, TSN.
authors.affiliation: Department of Plant Biology and Forest Genetics, Uppsala BioCenter, Swedish University of Agricultural Sciences, Box 7080, SE-75007 Uppsala, Sweden.
authors.forename: Jens F
authors.initials: JF
authors.lastname: Sundström
authors.forename: Alena
authors.initials: A
authors.lastname: Vaculova
authors.forename: Andrei P
authors.initials: AP
authors.lastname: Smertenko
authors.forename: Eugene I
authors.initials: EI
authors.lastname: Savenkov
authors.forename: Anna
authors.initials: A
authors.lastname: Golovko
authors.forename: Elena
authors.initials: E
authors.lastname: Minina
authors.forename: Budhi S
authors.initials: BS
authors.lastname: Tiwari
authors.forename: Salvador
authors.initials: S
authors.lastname: Rodriguez-Nieto
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Zamyatnin
authors.forename: Tuuli
authors.initials: T
authors.lastname: Välineva
authors.forename: Juha
authors.initials: J
authors.lastname: Saarikettu
authors.forename: Mikko J
authors.initials: MJ
authors.lastname: Frilander
authors.forename: Maria F
authors.initials: MF
authors.lastname: Suarez
authors.forename: Anton
authors.initials: A
authors.lastname: Zavialov
authors.forename: Ulf
authors.initials: U
authors.lastname: Ståhl
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hussey
authors.forename: Olli
authors.initials: O
authors.lastname: Silvennoinen
authors.forename: Eva
authors.initials: E
authors.lastname: Sundberg
authors.forename: Boris
authors.initials: B
authors.lastname: Zhivotovsky
authors.forename: Peter V
authors.initials: PV
authors.lastname: Bozhkov
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D004720:Endonucleases; D019143:Evolution, Molecular; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference
chemical_list: D009687:Nuclear Proteins; D004720:Endonucleases; C095221:SND1 protein, human