Tudor staphylococcal nuclease is an evolutionarily conserved component of the programmed cell death degradome

• Published in: Nature cell biology Vol. 11; no. 11; pp. 1347 - 1354
• Main Authors: Saarikettu, Juha, Suarez, Maria F, Tiwari, Budhi S, Rodriguez-Nieto, Salvador, Sundström, Jens F, Golovko, Anna, Välineva, Tuuli, Smertenko, Andrei P, Vaculova, Alena, Sundberg, Eva, Hussey, Patrick J, Savenkov, Eugene I, Zamyatnin, Andrey A, Minina, Elena, Frilander, Mikko J, Ståhl, Ulf, Silvennoinen, Olli, Bozhkov, Peter V, Zhivotovsky, Boris, Zavialov, Anton
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-11-2009; Nature Publishing Group
• Subjects: Animals; Apoptosis; Apoptosis - physiology; Biomedical and Life Sciences; Cancer Research; Cell and Molecular Biology; Cell Biology; Cell death; Cell- och molekylärbiologi; Developmental Biology; Evolution, Molecular; Fertility; Gene expression; Gene Knockdown Techniques; HeLa Cells; Humans; Hydrolysis; letter; Life Sciences; Medicin och hälsovetenskap; Models, Molecular; Mortality; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Physiological aspects; Proteases; Ribonuclease; RNA Interference; Stem Cells; Substrates; United Kingdom; Sweden; Finland
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/ncb1979

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.