A dedicated diribonucleotidase resolves a key bottleneck as the terminal step of RNA degradation
- University of Maryland, United States
- Cornell University, United States
Abstract
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.
Data availability
The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID codes 6N6A, 6N6C, 6N6D, 6N6E, 6N6F, 6N6G, 6N6H, 6N6I, 6N6J, and 6N6K). Source data files have been provided for Figures.
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Vibrio cholerae Oligoribonuclease bound to pGGProtein Data Bank, 6N6A.
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Vibrio cholerae Oligoribonuclease bound to pAAProtein Data Bank, 6N6C.
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Vibrio cholerae Oligoribonuclease bound to pAGProtein Data Bank, 6N6D.
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Vibrio cholerae Oligoribonuclease bound to pGAProtein Data Bank, 6N6E.
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Vibrio cholerae Oligoribonuclease bound to pGCProtein Data Bank, 6N6F.
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Vibrio cholerae Oligoribonuclease bound to pCGProtein Data Bank, 6N6G.
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Vibrio cholerae Oligoribonuclease bound to pCpUProtein Data Bank, 6N6H.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (R01AI110740)
- Vincent T Lee
National Institute of General Medical Sciences (R01GM123609)
- Holger Sondermann
National Science Foundation (MCB1051440)
- Wade C Winkler
Cystic Fibrosis Foundation (LEE16G0)
- Vincent T Lee
National Institute of Diabetes and Digestive and Kidney Diseases (R01AI110740)
- Vincent T Lee
National Institute of General Medical Sciences (T32-GM080201)
- Cordelia A Weiss
National Institute of Allergy and Infectious Diseases (R01AI142400)
- Wade C Winkler
- Holger Sondermann
- Vincent T Lee
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bryce E Nickels, Rutgers University, United States
Publication history
- Received: February 22, 2019
- Accepted: June 14, 2019
- Accepted Manuscript published: June 21, 2019 (version 1)
- Version of Record published: July 8, 2019 (version 2)
- Version of Record updated: July 10, 2019 (version 3)
- Version of Record updated: July 16, 2019 (version 4)
- Version of Record updated: January 28, 2022 (version 5)
Copyright
© 2019, Kim et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A dedicated diribonucleotidase resolves a key bottleneck as the terminal step of RNA degradation
eLife 8:e46313.
https://doi.org/10.7554/eLife.46313
Further reading
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- Microbiology and Infectious Disease
The malaria parasite life cycle includes asexual replication in human blood, with a proportion of parasites differentiating to gametocytes required for transmission to mosquitoes. Commitment to differentiate into gametocytes, which is marked by activation of the parasite transcription factor ap2-g, is known to be influenced by host factors but a comprehensive model remains uncertain. Here, we analyze data from 828 children in Kilifi, Kenya with severe, uncomplicated, and asymptomatic malaria infection over 18 years of falling malaria transmission. We examine markers of host immunity and metabolism, and markers of parasite growth and transmission investment. We find that inflammatory responses associated with reduced plasma lysophosphatidylcholine levels are associated with markers of increased investment in parasite sexual reproduction (i.e. transmission investment) and reduced growth (i.e. asexual replication). This association becomes stronger with falling transmission and suggests that parasites can rapidly respond to the within-host environment, which in turn is subject to changing transmission.
