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RNA Structure

Untying knots with force

Nature Chemical Biology volume 17, pages 933–934 (2021)Cite this article

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RNA knot-like structures function as an efficient physical barrier to RNA exoribonucleases. Single-molecule mechanical manipulation is used to unfold these structures and unravel the cause of their unusual mechanical resistance from a different direction.

Xrn1-resistant RNAs (xrRNA), first discovered in the flaviviral RNAs, enforces unidirectional traffic control by preventing exoribonucleases from destroying the RNA from its 5′ end while allowing RNA-dependent RNA polymerases (RdRp) to replicate from its 3′ end1. xrRNA forms a knot-like structure, termed ‘ring-knot’, in which the 5′ end of an RNA strand threads through a ring formed around a three-way junction2. Though formed by base pairing and stacking and not a true topological knot, the ring-knot is mechanically strong. The ring-knot must use divalent cations to counter the high density of negative charges, especially where the thread and the ring meet. Zhao and Woodside3 used single-molecule force spectroscopy to investigate how these relatively weak noncovalent interactions give rise to a stable ring-knot with directional nuclease resistance.

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Fig. 1: Two methods to mechanically untie a knot.

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  1. Department of Biological Sciences and The RNA Institute, University at Albany, SUNY, Albany, New York, USA

    Pan T. X. Li

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  1. Pan T. X. Li
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Correspondence to Pan T. X. Li.

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Li, P.T.X. Untying knots with force. Nat Chem Biol 17, 933–934 (2021). https://doi.org/10.1038/s41589-021-00856-w

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