Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 25, Pages 6404-6409Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1802429115
Keywords
noncoding RNA maturation; RNA structure; RNA dynamics; single-molecule FRET; exoribonuclease resistance
Categories
Funding
- National Institutes of Health [R35GM118070, R01 AI133348, F32GM117730, P30CA046934, S10OD012033]
- European Molecular Biology Laboratory [ALTF 611-2015]
- Office of Science, Office of Basic Energy Sciences of the US Department of Energy [DE-AC02-05CH11231]
- North Carolina Agricultural Research Service in the College of Agriculture and Life Sciences at North Carolina State University
- NATIONAL CANCER INSTITUTE [P30CA046934] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI133348] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [F32GM117730, R35GM118070] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [S10OD012033] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Folded RNA elements that block processive 5' -> 3' cellular exor-ibonucleases (xrRNAs) to produce biologically active viral noncoding RNAs have been discovered in flaviviruses, potentially revealing a new mode of RNA maturation. However, whether this RNA structure-dependent mechanism exists elsewhere and, if so, whether a singular RNA fold is required, have been unclear. Here we demonstrate the existence of authentic RNA structure-dependent xrRNAs in dianthoviruses, plant-infecting viruses unrelated to animal-infecting flaviviruses. These xrRNAs have no sequence similarity to known xrRNAs; thus, we used a combination of biochemistry and virology to characterize their sequence requirements and mechanism of stopping exoribonucleases. By solving the structure of a dianthovirus xrRNA by X-ray crystallography, we reveal a complex fold that is very different from that of the flavivirus xrRNAs. However, both versions of xrRNAs contain a unique topological feature, a pseudo-knot that creates a protective ring around the 5' end of the RNA structure; this may be a defining structural feature of xrRNAs. Single-molecule FRET experiments reveal that the dianthovirus xrRNAs undergo conformational changes and can use codegradational remodeling, exploiting the exoribonucleases' degradation-linked helicase activity to help form their resistant structure; such a mechanism has not previously been reported. Convergent evolution has created RNA structure-dependent exoribonuclease resistance in different contexts, which establishes it as a general RNA maturation mechanism and defines xrRNAs as an authentic functional class of RNAs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available