Abstract
Author SummaryIn addition to carrying genetic information from DNA to protein, RNAs function in many essential cellular processes. This often requires the RNA to form a specific three-dimensional structure, and some functions require cycling between multiple structures. However, RNAs have a strong propensity to become trapped in nonfunctional, misfolded structures. Due to the intrinsic stability of local structure for RNA, these misfolded species can be long-lived and therefore accumulate. ATP-dependent RNA chaperone proteins called DEAD-box proteins are known to promote native RNA folding by disrupting misfolded structures. Although these proteins can unwind short RNA helices, the mechanism by which they act upon higher order tertiary contacts is unknown. Our current work shows that DEAD-box proteins capture transiently exposed RNA helices, preventing any tertiary contacts from reforming and potentially destabilizing the global RNA architecture. Helix unwinding by the DEAD-box protein then allows the product RNA strands to form new contacts. This helix capture mechanism for manipulation of RNA tertiary structure does not require a specific binding motif or structural environment and may be general for DEAD-box helicase proteins that act on structured RNAs.
Highlights
Structured RNAs are involved in many essential biological processes such as pre-mRNA splicing, regulation of gene expression, protein synthesis, and maintenance of chromosome ends [1,2,3,4,5]
ATP-dependent RNA chaperone proteins called DEAD-box proteins are known to promote native RNA folding by disrupting misfolded structures
Our current work shows that DEADbox proteins capture transiently exposed RNA helices, preventing any tertiary contacts from reforming and potentially destabilizing the global RNA architecture
Summary
Structured RNAs are involved in many essential biological processes such as pre-mRNA splicing, regulation of gene expression, protein synthesis, and maintenance of chromosome ends [1,2,3,4,5] These functions require the RNAs to fold into specific structures and, for some, to transition between functional conformations. RNAs have a strong propensity for misfolding, and because RNA structure is inherently stable, even at the local level, resolution of misfolded RNAs or rearrangements of structured RNAs can be slow on the biological timescale These properties suggest a general requirement for RNA folding chaperones in vivo [6], and diverse proteins have been shown to possess ATP-dependent or ATP-independent RNA chaperone activity [7,8]. It has been proposed that regulated binding to single-stranded RNA (ssRNA) might be sufficient to accelerate disruption of tertiary contacts [22], such disruptions have not been demonstrated for any DEAD-box protein, leaving the mechanisms of these RNA remodeling reactions unclear
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