4.8 Article

Structural characterization of NrnC identifies unifying features of dinucleotidases

Journal

ELIFE
Volume 10, Issue -, Pages -

Publisher

eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.70146

Keywords

RNases; enzyme mechanism; dinucleotides; Bartonella henselae; Brucella melitensis; Pseudomonas aeruginosa; Other

Categories

Funding

  1. National Institutes of Health [R01AI142400, R01GM123609, R35GM136258]

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RNA degradation is crucial for cellular homeostasis, with nano-RNases and NrnC-type RNases playing unique roles in this process. These enzymes exhibit narrow substrate preferences and have evolved distinct structural features to maintain dinucleotidase activity, highlighting their important role in cell growth.
RNA degradation is fundamental for cellular homeostasis. The process is carried out by various classes of endolytic and exolytic enzymes that together degrade an RNA polymer to mono-ribonucleotides. Within the exoribonucleases, nano-RNases play a unique role as they act on the smallest breakdown products and hence catalyze the final steps in the process. We recently showed that oligoribonuclease (Orn) acts as a dedicated diribonucleotidase, defining the ultimate step in RNA degradation that is crucial for cellular fitness (Kim et al., 2019). Whether such a specific activity exists in organisms that lack Orn-type exoribonucleases remained unclear. Through quantitative structure-function analyses, we show here that NrnC-type RNases share this narrow substrate length preference with Orn. Although NrnC and Orn employ similar structural features that distinguish these two classes of dinucleotidases from other exonucleases, the key determinants for dinucleotidase activity are realized through distinct structural scaffolds. The structures, together with comparative genomic analyses of the phylogeny of DEDD-type exoribonucleases, indicate convergent evolution as the mechanism of how dinucleotidase activity emerged repeatedly in various organisms. The evolutionary pressure to maintain dinucleotidase activity further underlines the important role these analogous proteins play for cell growth.

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