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A dedicated diribonucleotidase resolves a key bottleneck for the terminal step of RNA degradation.

eLife | 2019

Degradation of RNA polymers, an ubiquitous process in all cells, is catalyzed by specific subsets of endo- and exoribonucleases that together recycle RNA fragments into nucleotide monophosphate. In γ-proteobacteria, 3-'5' exoribonucleases comprise up to eight distinct enzymes. Among them, Oligoribonuclease (Orn) is unique as its activity is required for clearing short RNA fragments, which is important for cellular fitness. However, the molecular basis of Orn's unique cellular function remained unclear. Here, we show that Orn exhibits exquisite substrate preference for diribonucleotides. Crystal structures of substrate-bound Orn reveal an active site optimized for diribonucleotides. While other cellular RNases process oligoribonucleotides down to diribonucleotide entities, Orn is the one and only diribonucleotidase that completes the terminal step of RNA degradation. Together, our studies indicate RNA degradation as a step-wise process with a dedicated enzyme for the clearance of a specific intermediate pool, diribonucleotides, that affects cellular physiology and viability.

Pubmed ID: 31225796 RIS Download

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: P30 GM124166
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI142400
  • Agency: Cystic Fibrosis Foundation, International
    Id: LEE16G0
  • Agency: NIGMS NIH HHS, United States
    Id: T32-GM080201
  • Agency: National Institute of Allergy and Infectious Diseases, International
    Id: R01AI142400
  • Agency: NIGMS NIH HHS, United States
    Id: P41 GM103485
  • Agency: National Institute of Allergy and Infectious Diseases, International
    Id: R01AI110740
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM123609
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI110740
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI089621
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM080201
  • Agency: NIGMS NIH HHS, United States
    Id: R01GM123609
  • Agency: National Science Foundation, International
    Id: MCB1051440

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