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

Jens F. Sundstrom, Alena Vaculova, Andrei P. Smertenko, Eugene I. Savenkov, Anna Golovko, Elena Minina, Budhi S. Tiwari, Salvador Rodriguez-Nieto, Andrey A. Zamyatnin Jr, Tuuli Välineva, Juha Saarikettu, Mikko J. Frilander, Maria F. Suarez, Anton Zavialov, Ulf Ståhl, Patrick J. Hussey, Olli Silvennoinen, Eva Sundberg, Boris Zhivotovsky, Peter V. Bozhkov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

159 Citations (Scopus)


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(1,2). Plants lack close homologues of caspases, but instead possess an ancestral family of cysteine proteases, metacaspases(3,4). Although metacaspases are essential for PCD(5-7), their natural substrates remain unknown(4,8). 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(9-15), 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.

Original languageEnglish
Pages (from-to)1347-U198
Number of pages17
JournalNature Cell Biology
Issue number11
Publication statusPublished - Nov 2009


  • RNA
  • DNA


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