Research Progress of RNA Quadruplex

Ji, Xiaohui; Sun, Hongxia; Zhou, Huaxi; Xiang, Junfeng; Tang, Yalin; Zhao, Changqi

doi:10.1089/nat.2010.0272

Cited by 48 publications

(37 citation statements)

References 107 publications

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“…This region contains one of five 3G stretches in human 7SK (9-11, 50–52, 81–83, 188–190 and 262–264), all of which are conserved from human through frogs and four that are conserved through fish (Supplementary Figure S3). RNA G-quadruplexes form by the arrangement of the triplets so that there is a stack of three groups of four planer guanines (63–65). The G-quadruplex structure is stabilized by cations that are coordinated with the bases and between the planes.…”

Section: Resultsmentioning

confidence: 99%

Reconstitution of a functional 7SK snRNP

Brogie

Price

2017

Nucleic Acids Research

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The 7SK small nuclear ribonucleoprotein (snRNP) plays a central role in RNA polymerase II elongation control by regulating the availability of active P-TEFb. We optimized conditions for analyzing 7SK RNA by SHAPE and demonstrated a hysteretic effect of magnesium on 7SK folding dynamics including a 7SK GAUC motif switch. We also found evidence that the 5΄ end pairs alternatively with two different regions of 7SK giving rise to open and closed forms that dictate the state of the 7SK motif. We then used recombinant P-TEFb, HEXIM1, LARP7 and MEPCE to reconstruct a functional 7SK snRNP in vitro. Stably associated P-TEFb was highly inhibited, but could still be released and activated by HIV-1 Tat. Notably, P-TEFb association with both in vitro-reconstituted and cellular snRNPs led to similar changes in SHAPE reactivities, confirming that 7SK undergoes a P-TEFb-dependent structural change. We determined that the xRRM of LARP7 binds to the 3΄ stem loop of 7SK and inhibits the methyltransferase activity of MEPCE through a C-terminal MEPCE interaction domain (MID). Inhibition of MEPCE is dependent on the structure of the 3΄ stem loop and the closed form of 7SK RNA. This study provides important insights into intramolecular interactions within the 7SK snRNP.

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Section: Resultsmentioning

confidence: 99%

Reconstitution of a functional 7SK snRNP

Brogie

Price

2017

Nucleic Acids Research

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“…G-quadruplex motifs in RNA have only come into the focus of research in recent years (2,6,7,9). They have been reported to be involved in regulation of translation and to have a function in splicing (9).…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of RNA guanine-quadruplex binding proteins

Hacht

Seifert

Menger

et al. 2014

Nucleic Acids Research

108

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Guanine quadruplex (G-quadruplex) motifs in the 5′ untranslated region (5′-UTR) of mRNAs were recently shown to influence the efficiency of translation. In the present study, we investigate the interaction between cellular proteins and the G-quadruplexes located in two mRNAs (MMP16 and ARPC2). Formation of the G-quadruplexes was confirmed by biophysical characterization and the inhibitory activity on translation was shown by luciferase reporter assays. In experiments with whole cell extracts from different eukaryotic cell lines, G-quadruplex-binding proteins were isolated by pull-down assays and subsequently identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The binding partners of the RNA G-quadruplexes we discovered included several heterogenous nuclear ribonucleoproteins, ribosomal proteins, and splicing factors, as well as other proteins that have previously not been described to interact with nucleic acids. While most of the proteins were specific for either of the investigated G-quadruplexes, some of them bound to both motifs. Selected candidate proteins were subsequently produced by recombinant expression and dissociation constants for the interaction between the proteins and RNA G-quadruplexes in the low nanomolar range were determined by surface plasmon resonance spectroscopy. The present study may thus help to increase our understanding of the mechanisms by which G-quadruplexes regulate translation.

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“…Recently, it was shown that G-quadruplexes in RNA play a role in various cellular functions including termination of transcription, telomerase activity, alternative splicing and modulation of translation [123,124]. Using the pull-down assay, a set of proteins involved in interaction with RNA G-quadruplexes was identified and characterized, including hnRNP, ribosomal proteins, splicing factors and others [69].…”

Section: Proteins Involved In Interactions With Quadruplex Dnamentioning

confidence: 99%

DNA and RNA Quadruplex-Binding Proteins

Brázda

Hároníková

Liao

et al. 2014

IJMS

220

180

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Four-stranded DNA structures were structurally characterized in vitro by NMR, X-ray and Circular Dichroism spectroscopy in detail. Among the different types of quadruplexes (i-Motifs, minor groove quadruplexes, G-quadruplexes, etc.), the best described are G-quadruplexes which are featured by Hoogsteen base-paring. Sequences with the potential to form quadruplexes are widely present in genome of all organisms. They are found often in repetitive sequences such as telomeric ones, and also in promoter regions and 5' non-coding sequences. Recently, many proteins with binding affinity to G-quadruplexes have been identified. One of the initially portrayed G-rich regions, the human telomeric sequence (TTAGGG)n, is recognized by many proteins which can modulate telomerase activity. Sequences with the potential to form G-quadruplexes are often located in promoter regions of various oncogenes. The NHE III1 region of the c-MYC promoter has been shown to interact with nucleolin protein as well as other G-quadruplex-binding proteins. A number of G-rich sequences are also present in promoter region of estrogen receptor alpha. In addition to DNA quadruplexes, RNA quadruplexes, which are critical in translational regulation, have also been predicted and observed. For example, the RNA quadruplex formation in telomere-repeat-containing RNA is involved in interaction with TRF2 (telomere repeat binding factor 2) and plays key role in telomere regulation. All these fundamental examples suggest the importance of quadruplex structures in cell processes and their understanding may provide better insight into aging and disease development.

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Research Progress of RNA Quadruplex

Cited by 48 publications

References 107 publications

Reconstitution of a functional 7SK snRNP

Reconstitution of a functional 7SK snRNP

Identification and characterization of RNA guanine-quadruplex binding proteins

DNA and RNA Quadruplex-Binding Proteins

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