Unraveling the structure and biological functions of <scp>RNA</scp> triple helices

Brown, Jessica A.

doi:10.1002/wrna.1598

Cited by 62 publications

(46 citation statements)

References 214 publications

(406 reference statements)

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“…2c). This local triplebase configuration obtained is similar to arginine sandwich motifs 31 . Overall, with continuous stacking of all helices in the helix 1c configuration, the structure of SL-Au1 has a linear appearance (Fig.…”

Section: Structure Of the Au1 Elementsupporting

confidence: 73%

A novel structural mechanism of ribosomal stop codon readthrough in VEGF-A

Wagner

Edwards

Abramovich

et al. 2021

Preprint

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The process of ribosomal recoding is generally regulated by an autonomous mRNA signal downstream of stop-codons. While structural studies have provided mechanistic insights into viral systems, no such studies exist in mammalian systems. Here we define a novel structural mechanism for the VEGF-A readthrough system and show that regulation is multifaceted and complex, requiring a multipartite set of RNA elements located at long distances that interact with each other and with hnRNP A2/B1 to synergistically enhance readthrough levels. The Ax-element downstream of the stop codon adopts a unique multistem (SL-Ax1-3) architecture: SL-Ax1 interacts with hnRNP A2/B1, while SL-Ax2 interacts with an RNA element (SL-Au1) located ~500 nt upstream at the start of the coding sequence. SL-Au1 also independently binds to hnRNP A2/B1, which manipulates an equilibrium between alternate structures— from a sequestered bulge towards one that allows for the long-range interaction with SL-Ax2. Overall, our study not only highlights the significance of structural organization of elements within the coding sequence of mRNA, but also provides a functional relevance of the closed-loop mRNA organization in non-canonical translation and suggests complex mechanisms allow for finer integration of many signals for a required output.

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Section: Structure Of the Au1 Elementsupporting

confidence: 73%

A novel structural mechanism of ribosomal stop codon readthrough in VEGF-A

Wagner

Edwards

Abramovich

et al. 2021

Preprint

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“…Watson–Crick (WC) base pairs shape the RNA double-helical landscape. However, multiple non-WC interactions ( Leontis et al, 2002 ) have been distinguished in RNA structures and implicated in various biological functions of RNA ( Westhof and Fritsch, 2000 ; Chandrasekhar and Malathhi, 2003 ; Brown, 2020 ). The G•U wobble base pair is the most frequent among the non-WC base pairs in RNA molecules.…”

Section: Introductionmentioning

confidence: 99%

Structural Insights Into the 5′UG/3′GU Wobble Tandem in Complex With Ba2+ Cation

Ruszkowska

Zheng

Mao

et al. 2022

Front. Mol. Biosci.

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G•U wobble base pair frequently occurs in RNA structures. The unique chemical, thermodynamic, and structural properties of the G•U pair are widely exploited in RNA biology. In several RNA molecules, the G•U pair plays key roles in folding, ribozyme catalysis, and interactions with proteins. G•U may occur as a single pair or in tandem motifs with different geometries, electrostatics, and thermodynamics, further extending its biological functions. The metal binding affinity, which is essential for RNA folding, catalysis, and other interactions, differs with respect to the tandem motif type due to the different electrostatic potentials of the major grooves. In this work, we present the crystal structure of an RNA 8-mer duplex r[UCGUGCGA]2, providing detailed structural insights into the tandem motif I (5′UG/3′GU) complexed with Ba2+ cation. We compare the electrostatic potential of the presented motif I major groove with previously published structures of tandem motifs I, II (5′GU/3′UG), and III (5′GG/3′UU). A local patch of a strongly negative electrostatic potential in the major groove of the presented structure forms the metal binding site with the contributions of three oxygen atoms from the tandem. These results give us a better understanding of the G•U tandem motif I as a divalent metal binder, a feature essential for RNA functions.

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“…However, the dENE engages poly(A) in a 5ʹ-to-3ʹ direction (SI Appendix, Fig. S19) opposite to that established for PAN or MALAT1 lncRNAs (6,15,25). More interestingly, the dENE contains a pocket motif, whose formation relies on long-range interactions between A-triad nucleotides (bulged A11 in the lower stem, A67 and A68 in the lower URIL) (Fig.…”

Section: Discussionmentioning

confidence: 93%

Structural analyses of an RNA stability element interacting with poly(A)

Torabi

Chen

Zhang

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Cis-acting RNA elements are crucial for the regulation of polyadenylated RNA stability. The element for nuclear expression (ENE) contains a U-rich internal loop flanked by short helices. An ENE stabilizes RNA by sequestering the poly(A) tail via formation of a triplex structure that inhibits a rapid deadenylation-dependent decay pathway. Structure-based bioinformatic studies identified numerous ENE-like elements in evolutionarily diverse genomes, including a subclass containing two ENE motifs separated by a short double-helical region (double ENEs [dENEs]). Here, the structure of a dENE derived from a rice transposable element (TWIFB1) before and after poly(A) binding (∼24 kDa and ∼33 kDa, respectively) is investigated. We combine biochemical structure probing, small angle X-ray scattering (SAXS), and cryo‐electron microscopy (cryo-EM) to investigate the dENE structure and its local and global structural changes upon poly(A) binding. Our data reveal 1) the directionality of poly(A) binding to the dENE, and 2) that the dENE-poly(A) interaction involves a motif that protects the 3ʹ-most seven adenylates of the poly(A). Furthermore, we demonstrate that the dENE does not undergo a dramatic global conformational change upon poly(A) binding. These findings are consistent with the recently solved crystal structure of a dENE+poly(A) complex [S.-F. Torabi et al., Science 371, eabe6523 (2021)]. Identification of additional modes of poly(A)–RNA interaction opens new venues for better understanding of poly(A) tail biology.

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Unraveling the structure and biological functions of RNA triple helices

Cited by 62 publications

References 214 publications

A novel structural mechanism of ribosomal stop codon readthrough in VEGF-A

A novel structural mechanism of ribosomal stop codon readthrough in VEGF-A

Structural Insights Into the 5′UG/3′GU Wobble Tandem in Complex With Ba2+ Cation

Structural analyses of an RNA stability element interacting with poly(A)

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