Selecting New RNA Crystal Contacts

Gomez, Anastassia; Toor, Navtej

doi:10.1016/j.str.2018.08.009

Cited by 6 publications

(6 citation statements)

References 5 publications

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“…By contrast, X-ray crystallography is, in principle, applicable to large macromolecules. However, X-ray crystallography for RNA is more challenging than for proteins, particularly with respect to construct engineering for obtaining well-diffracting crystals (Wiryaman and Toor 2017;Gomez and Toor 2018) and to phasing (Marcia et al 2013;Marcia 2016). Except for the ribosome, the spliceosome, RNase P, and group I and II introns (Pyle 2014), RNA crystal structures are available only for short molecules (<200 nt long).…”

Section: High-resolution Methodsmentioning

confidence: 99%

The molecular structure of long non-coding RNAs: emerging patterns and functional implications

Chillón

Marcia

2020

Critical Reviews in Biochemistry and Molecular Biology

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Long non-coding RNAs (lncRNAs) are recently-discovered transcripts that regulate vital cellular processes and are crucially connected to diseases. Despite their unprecedented molecular complexity, it is emerging that lncRNAs possess distinct structural motifs. Remarkably, the 3D shape and topology of full-length, native lncRNAs have been visualized for the first time in the last year. These studies reveal that lncRNA structures dictate lncRNA functions. Here, we review experimentally determined lncRNA structures and emphasize that lncRNA structural characterization requires synergistic integration of computational, biochemical and biophysical approaches. Based on these emerging paradigms, we discuss how to overcome the challenges posed by the complex molecular architecture of lncRNAs, with the goal of obtaining a detailed understanding of lncRNA functions and molecular mechanisms in the future.

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Section: High-resolution Methodsmentioning

confidence: 99%

The molecular structure of long non-coding RNAs: emerging patterns and functional implications

Chillón

Marcia

2020

Critical Reviews in Biochemistry and Molecular Biology

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“…Macromolecular structures can be directly measured, simulated, or derived from sequence by solving the folding problem ( 4 ), using computational tools ( 5 ), or applying artificial intelligence ( 6 ). Because of the highly charged and dynamic nature of its backbone, as well as the similarity of its nucleotide building blocks, RNA structures are far more challenging to solve than protein structures, by either experiment ( 7 – 9 ) or all-atom simulation ( 10 , 11 ) The paucity of measured structures limits our ability to advance the field ( 12 ), especially when compared to the state of the art in protein structure prediction ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

RNA structures and dynamics with Å resolution revealed by x-ray free-electron lasers

Zielinski,

Sui,

Pabit

et al. 2023

Sci. Adv.

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RNA macromolecules, like proteins, fold to assume shapes that are intimately connected to their broadly recognized biological functions; however, because of their high charge and dynamic nature, RNA structures are far more challenging to determine. We introduce an approach that exploits the high brilliance of x-ray free-electron laser sources to reveal the formation and ready identification of angstrom-scale features in structured and unstructured RNAs. Previously unrecognized structural signatures of RNA secondary and tertiary structures are identified through wide-angle solution scattering experiments. With millisecond time resolution, we observe an RNA fold from a dynamically varying single strand through a base-paired intermediate to assume a triple-helix conformation. While the backbone orchestrates the folding, the final structure is locked in by base stacking. This method may help to rapidly characterize and identify structural elements in nucleic acids in both equilibrium and time-resolved experiments.

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“…Macromolecular structures can be directly measured, simulated, or derived from sequence by solving the folding problem (4), using computational tools (5), or applying artificial intelligence (6). Because of the highly charged and dynamic nature of its backbone, as well as the similarity of its nucleotide building blocks, RNA structures are far more challenging to solve than protein structures, by either experiment (7)(8)(9) or all atom simulation (10,11) The paucity of measured structures limits our ability to advance the field (12), especially when compared to the state-ofthe-art in protein structure prediction (6) .…”

Section: Introductionmentioning

confidence: 99%

RNA structures and dynamics with Å resolution revealed by x-ray free electron lasers

Zielinski

Sui

Pabit

et al. 2023

Preprint

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RNA macromolecules, like proteins, fold to assume shapes that are intimately connected to their broadly recognized biological functions; however, because of their high charge and dynamic nature, RNA structures are far more challenging to determine. We introduce an approach that exploits the high brilliance of x-ray free electron laser sources to reveal the formation and ready identification of Å scale features in structured and unstructured RNAs. New structural signatures of RNA secondary and tertiary structures are identified through wide angle solution scattering experiments. With millisecond time resolution, we observe an RNA fold from a dynamically varying single strand through a base paired intermediate to assume a triple helix conformation. While the backbone orchestrates the folding, the final structure is locked in by base stacking. In addition to understanding how RNA triplexes form and thereby function as dynamic signaling elements, this new method can vastly increase the rate of structure determination for these biologically essential, but mostly uncharacterized macromolecules.

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Selecting New RNA Crystal Contacts

Abstract: RNAs are relatively difficult to crystallize because many sequence variants must be tested to obtain suitable crystal contacts. In this issue of Structure, Shoffner et al. (2018) report an in crystallo selection procedure that allows for the rapid generation of new RNA crystal contacts.

Cited by 6 publications

References 5 publications

The molecular structure of long non-coding RNAs: emerging patterns and functional implications

The molecular structure of long non-coding RNAs: emerging patterns and functional implications

RNA structures and dynamics with Å resolution revealed by x-ray free-electron lasers

RNA structures and dynamics with Å resolution revealed by x-ray free electron lasers

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