A shape-shifting nuclease unravels structured RNA

Meze, Katarina, Axhemi, Armend, Thomas, Dennis R, Doymaz, Ahmet, Joshua-Tor, Leemor (February 2023) A shape-shifting nuclease unravels structured RNA. Nature Structural and Molecular Biology. ISSN 1545-9993

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Abstract

RNA turnover pathways ensure appropriate gene expression levels by eliminating unwanted transcripts. Dis3-like 2 (Dis3L2) is a 3'-5' exoribonuclease that plays a critical role in human development. Dis3L2 independently degrades structured substrates, including coding and noncoding 3' uridylated RNAs. While the basis for Dis3L2's substrate recognition has been well characterized, the mechanism of structured RNA degradation by this family of enzymes is unknown. We characterized the discrete steps of the degradation cycle by determining cryogenic electron microscopy structures representing snapshots along the RNA turnover pathway and measuring kinetic parameters for RNA processing. We discovered a dramatic conformational change that is triggered by double-stranded RNA (dsRNA), repositioning two cold shock domains by 70 Å. This movement exposes a trihelix linker region, which acts as a wedge to separate the two RNA strands. Furthermore, we show that the trihelix linker is critical for dsRNA, but not single-stranded RNA, degradation. These findings reveal the conformational plasticity of Dis3L2 and detail a mechanism of structured RNA degradation.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA expression Investigative techniques and equipment > microscopy > electron microscopy bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > ribonuclease
CSHL Authors:	Meze, Katarina Axhemi, Armend Thomas, Dennis R Joshua-Tor, Leemor
Communities:	CSHL labs > Furukawa lab CSHL labs > Joshua-Tor lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	23 February 2023
Date Deposited:	28 Feb 2023 18:36
Last Modified:	28 Feb 2023 18:36
URI:	https://repository.cshl.edu/id/eprint/40846

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