Computational design of three-dimensional RNA structure and function

Yesselman, Joseph D.; Eiler, Daniel; Carlson, Erik D.; Gotrik, Michael R.; d’Aquino, Anne E.; Ooms, Alexandra N.; Kladwang, Wipapat; Carlson, Paul D.; Shi, Xianzhe; Costantino, David A.; Herschlag, Daniel; Lucks, Julius B.; Jewett, Michael C.; Kieft, Jeffrey S.; Das, Rhiju

doi:10.1038/s41565-019-0517-8

Cited by 69 publications

(56 citation statements)

References 58 publications

(73 reference statements)

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“…Both structures brought valuable insights into the function of THF riboswitch and led to the design of artificial homodimeric RNAs responsive to THF through a loop-receptor intermolecular interface [ 159 ]. Similar artificial constructs were previously formed through a GAAA tetraloop-receptor mediated homodimerization interface [ 151 , 152 , 160 ].…”

Section: Homodimerization Of Riboswitchesmentioning

confidence: 99%

“…That means the donors (A-rich bulge or loop) and receptors (minor groove of G-C/C-G pairs) of the A-minor interactions were spaced and angled in such a way that two oppositely oriented copies of the aptamer can simultaneously engage two sets of A-minor interactions with each other, thereby seeding the dimer configuration. This notion is analogous to the design of a dimer tectoRNA, which took advantage of appropriately spaced tetraloop and tetraloop receptor motifs, achieving a dimerization K d of ~4 nM [ 151 , 152 , 153 ]. The resulting mutual reinforcement of both glycine-binding aptamers, clearly advantageous for folding, overall stability, and possibly also tighter binding of small ligands, such as glycine, led to retention of the dimeric form.…”

Section: Homodimerization Of Riboswitchesmentioning

confidence: 99%

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Structural Insights into RNA Dimerization: Motifs, Interfaces and Functions

Bou‐Nader

Zhang

2020

Molecules

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In comparison with the pervasive use of protein dimers and multimers in all domains of life, functional RNA oligomers have so far rarely been observed in nature. Their diminished occurrence contrasts starkly with the robust intrinsic potential of RNA to multimerize through long-range base-pairing (“kissing”) interactions, self-annealing of palindromic or complementary sequences, and stable tertiary contact motifs, such as the GNRA tetraloop-receptors. To explore the general mechanics of RNA dimerization, we performed a meta-analysis of a collection of exemplary RNA homodimer structures consisting of viral genomic elements, ribozymes, riboswitches, etc., encompassing both functional and fortuitous dimers. Globally, we found that domain-swapped dimers and antiparallel, head-to-tail arrangements are predominant architectural themes. Locally, we observed that the same structural motifs, interfaces and forces that enable tertiary RNA folding also drive their higher-order assemblies. These feature prominently long-range kissing loops, pseudoknots, reciprocal base intercalations and A-minor interactions. We postulate that the scarcity of functional RNA multimers and limited diversity in multimerization motifs may reflect evolutionary constraints imposed by host antiviral immune surveillance and stress sensing. A deepening mechanistic understanding of RNA multimerization is expected to facilitate investigations into RNA and RNP assemblies, condensates, and granules and enable their potential therapeutical targeting.

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Section: Homodimerization Of Riboswitchesmentioning

confidence: 99%

Section: Homodimerization Of Riboswitchesmentioning

confidence: 99%

Structural Insights into RNA Dimerization: Motifs, Interfaces and Functions

Bou‐Nader

Zhang

2020

Molecules

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“…Mostly, these structures correspond to short RNAs or RNA fragments of <200 nt in length. Thus, despite ongoing efforts, current de novo RNA 3D structure prediction are accurate only for short segments (Hajdin et al 2010;Humphris-Narayanan and Pyle 2012;Magnus et al 2019;Yesselman et al 2019;Watkins et al 2020).…”

Section: Challenges In Lncrna Structural Studiesmentioning

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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“…[27][28][29][30] Similar exciting advances are to be expected in the field of nucleic acids research. 31,32 This review summarizes recent developments in the fields of in vitro selected fluorogenic RNA aptamers and riboswitch discovery, and discusses more intensively the structures and mechanistic elucidations of recently discovered natural ribozymes, which we contrast with in vitro selected DNAzymes catalysing phosphodiester cleavage and ligation chemistry ( Fig. 1).…”

Section: Introductionmentioning

confidence: 99%