PNPT1 Release from Mitochondria during Apoptosis Triggers Decay of Poly(A) RNAs

• Xing Liu ^[1] ; Rui Fu ^[1] ; Youdong Pan ^[2]
  1. [1] Boston Children´s Hospital
  2. [2] Brigham and Women´s Hospital
• Localización: Cell, ISSN 0092-8674, Vol. 174, Nº. 1, 2018, págs. 187-201
• Idioma: inglés
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• Resumen

  • Widespread mRNA decay, an unappreciated feature of apoptosis, enhances cell death and depends on mitochondrial outer membrane permeabilization (MOMP), TUTases, and DIS3L2. Which RNAs are decayed and the decay-initiating event are unknown. Here, we show extensive decay of mRNAs and poly(A) noncoding (nc)RNAs at the 3′ end, triggered by the mitochondrial intermembrane space 3′-to-5′ exoribonuclease PNPT1, released during MOMP. PNPT1 knockdown inhibits apoptotic RNA decay and reduces apoptosis, while ectopic expression of PNPT1, but not an RNase-deficient mutant, increases RNA decay and cell death. The 3′ end of PNPT1 substrates thread through a narrow channel. Many non-poly(A) ncRNAs contain 3′-secondary structures or bind proteins that may block PNPT1 activity. Indeed, mutations that disrupt the 3′-stem-loop of a decay-resistant ncRNA render the transcript susceptible, while adding a 3′-stem-loop to an mRNA prevents its decay. Thus, PNPT1 release from mitochondria during MOMP initiates apoptotic decay of RNAs lacking 3′-structures.