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Nanomanipulation of Single RNA Molecules by Optical Tweezers
Published on: August 20, 2014
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A shape-shifting nuclease unravels structured RNA
Katarina Meze1,2,3, Armend Axhemi1,3, Dennis R Thomas1,3
1W.M. Keck Structural Biology Laboratory, Howard Hughes Medical Institute, New York, NY, USA.
Nature Structural & Molecular Biology
|February 24, 2023
Summary
Dis3-like 2 (Dis3L2) degrades structured RNAs by undergoing a dramatic conformational change. This exoribonuclease uses a trihelix linker to separate double-stranded RNA, revealing its degradation mechanism.
Area of Science:
- Molecular Biology
- Biochemistry
- Structural Biology
Background:
- RNA turnover is crucial for regulating gene expression.
- Dis3-like 2 (Dis3L2) is a 3'-5' exoribonuclease vital for human development.
- Dis3L2 degrades structured RNAs, but its degradation mechanism is unknown.
Purpose of the Study:
- To elucidate the mechanism of structured RNA degradation by Dis3L2.
- To characterize the conformational changes and kinetic parameters involved in Dis3L2's RNA processing.
Main Methods:
- Cryogenic electron microscopy (cryo-EM) to determine structures at different stages of RNA degradation.
- Kinetic analysis to measure RNA processing rates.
- Biochemical assays to assess the role of specific protein regions.
Main Results:
- Dis3L2 undergoes a significant conformational change upon binding double-stranded RNA (dsRNA).
- This conformational change repositions cold shock domains and exposes a trihelix linker region.
- The trihelix linker acts as a wedge to separate dsRNA strands and is essential for dsRNA degradation.
- Dis3L2's degradation of single-stranded RNA does not involve this mechanism.
Conclusions:
- Dis3L2 exhibits conformational plasticity, enabling structured RNA degradation.
- A novel mechanism involving a trihelix linker wedge is revealed for dsRNA processing by Dis3L2.
- These findings provide critical insights into the function of Dis3L2 in RNA turnover and human development.
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