The mitochondrial ARTS protein promotes apoptosis through targeting XIAP

ARTS is an unusual septin-like mitochondrial protein that was originally shown to mediate TGF-beta-induced apoptosis. Recently, we found that ARTS is also important for cell killing by other pro-apoptotic factors, such as arabinoside, etoposide, staurosporine and Fas. In Drosophila, the IAP antagonists Reaper, Hid and Grim are essential for the induction of virtually all apoptotic cell death. We found that mutations in peanut, which encodes a Drosophila homologue of ARTS, can dominantly suppress cell killing by Reaper, Hid and Grim, indicating that peanut acts downstream or in parallel to these. In mammalian cells, ARTS is released from mitochondria upon pro-apoptotic stimuli and then binds to XIAP. Binding of ARTS to XIAP is direct, as recombinant ARTS and XIAP proteins can bind to each other in vitro. ARTS binding to XIAP is specific and related to its pro-apoptotic function, as mutant forms of ARTS (or related septins) that fail to bind XIAP failed to induce apoptosis. ARTS leads to decreased XIAP protein levels and caspase activation. Our data suggest that ARTS induces apoptosis by antagonizing IAPs

Transcription in the nucleus and mRNA decay in the cytoplasm are coupled processes

Maintaining appropriate mRNAs levels is vital for any living cell. mRNA synthesis in the nucleus by RNA polymerase II core enzyme (Pol II) and mRNA decay by cytoplasmic machineries determine these levels. Yet, little is known about possible cross-talk between these processes. The yeast Rpb4/7 is a nucleo-cytoplasmic shuttling heterodimer that interacts with Pol II and with mRNAs and is required for mRNA decay in the cytoplasm. Here we show that interaction of Rpb4/7 with mRNAs and eventual decay of these mRNAs in the cytoplasm depends on association of Rpb4/7 with Pol II in the nucleus. We propose that, following its interaction with Pol II, Rpb4/7 functions in transcription, interacts with the transcript cotranscriptionally and travels with it to the cytoplasm to stimulate mRNA decay. Hence, by recruiting Rpb4/7, Pol II governs not only transcription but also mRNA decay

The RNA polymerase II subunit Rpb4p mediates decay of a specific class of mRNAs

It is commonly appreciated that the mRNA level is determined by the balance between its synthetic and decay kinetics. Yet, little is known about coordination between these distinct processes. A major pathway of the eukaryotic mRNA decay initiates with shortening of the mRNA poly(A) tail (deadenylation), followed by removal of the mRNA 5′ cap structure and its subsequent exonucleolytic degradation. Here we report that a subunit of RNA polymerase II, Rpb4p, is required for the decay of a class of mRNAs whose products are involved in protein synthesis. Cells lacking RPB4 are defective in the deadenylation and post-deadenylation steps of representatives of this class of mRNAs. Moreover, Rpb4p interacts with both the mRNP and with subunits of the mRNA decay complex Pat1/Lsm1–7 that enhances decapping. Consistently, a portion of Rpb4p is localized in P bodies, where mRNA decapping and degradation is executed, and mutations in RPB4 increase the number of P bodies per cell. We propose that Rpb4p has a dual function in mRNA decay. It promotes or enhances the deadenylation process of specific mRNAs and recruits Pat1/Lsm1–7 to these mRNAs, thus stimulating their decapping and further decay. In this way, Rpb4p might link the activity of the basal transcription apparatus with that of the mRNA decay machinery