The folding of 5′-UTR human G-quadruplexes possessing a long central loop

Jodoin, Rachel; Bauer, Ľuboš; Garant, Jean-Michel; Laaref, Abdelhamid Mahdi; Phaneuf, Francis; Perreault, Jean‐Pierre

doi:10.1261/rna.044578.114

Cited by 58 publications

(69 citation statements)

References 44 publications

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“…This was revised, when Beaudoin and Perreault (2010) identified 9,979 5′-UTRs to contain at least one pG4 sequence, among the 124,315 transcripts from the human UTRfull dataset based on a “regular” definition of G-quadruplex 48 . Subsequently, it was discovered that 1,453 human pG4 sequences possess 2 short distal loops of 1 nucleotide in length and a long central loop of up to 70 nucleotides long in the 5′-UTRs, which significantly expands the number of pG4s in the transcriptome 49 . A bioinformatic search for “regular” G-quadruplex in 3′-UTRs of the human transcriptome, detected 8,903 pG4 sequences showing that the enrichment for G-quadruplex is not limited to the 5′-UTRs 50 .…”

Section: Rna G-quadruplexesmentioning

confidence: 99%

RNA G-quadruplexes and their potential regulatory roles in translation

et al. 2016

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DNA guanine (G)-rich 4-stranded helical nucleic acid structures called G-quadruplexes (G4), have been extensively studied during the last decades. However, emerging evidence reveals that 5′- and 3′-untranslated regions (5′- and 3′-UTRs) as well as open reading frames (ORFs) contain putative RNA G-quadruplexes. These stable secondary structures play key roles in telomere homeostasis and RNA metabolism including pre-mRNA splicing, polyadenylation, mRNA targeting and translation. Interestingly, multiple RNA binding proteins such as nucleolin, FMRP, DHX36, and Aven were identified to bind RNA G-quadruplexes. Moreover, accumulating reports suggest that RNA G-quadruplexes regulate translation in cap-dependent and -independent manner. Herein, we discuss potential roles of RNA G-quadruplexes and associated trans-acting factors in the regulation of mRNA translation.

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Section: Rna G-quadruplexesmentioning

confidence: 99%

RNA G-quadruplexes and their potential regulatory roles in translation

et al. 2016

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“…BC200 RNAs were stored in phosphate-buffered saline (137 mM NaCl, 2.7 mM KCl, 10 mM Na 2 HPO 4 , 1.8 mM KH 2 PO 4 , pH 7.4). The PITX1 Q1, PITX1 Q1 Mut , PITX1 Q2, PITX1 Q3, hTR(10 -43), hTR (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), and 25P1 RNAs were purchased from Integrated DNA Technologies and were described previously (21,23).…”

Section: Rna Immunoprecipitation For Rt-pcr Analysis and Westernmentioning

confidence: 99%

“…A typical requirement for quadruplex formation is the presence of four tracts of three or more guanines that align in parallel or antiparallel strands with short (Ͻ7-nt) interspersed loops (6); however, quadruplexes with longer loops have also been reported (7,8). Quadruplexes have been shown to possess myriad roles in gene transcription and post-transcriptional regulation of both coding and non-coding RNAs (9 -16).…”

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confidence: 99%

RNA Helicase Associated with AU-rich Element (RHAU/DHX36) Interacts with the 3′-Tail of the Long Non-coding RNA BC200 (BCYRN1)

Booy¹,

McRae²,

Howard³

et al. 2016

Journal of Biological Chemistry

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RNA helicase associated with AU-rich element (RHAU) is an ATP-dependent RNA helicase that demonstrates high affinity for quadruplex structures in DNA and RNA. To elucidate the significance of these quadruplex-RHAU interactions, we have performed RNA co-immunoprecipitation screens to identify novel RNAs bound to RHAU and characterize their function. In the course of this study, we have identified the non-coding RNA BC200 (BCYRN1) as specifically enriched upon RHAU immunoprecipitation. Although BC200 does not adopt a quadruplex structure and does not bind the quadruplex-interacting motif of RHAU, it has direct affinity for RHAU in vitro. Specifically designed BC200 truncations and RNase footprinting assays demonstrate that RHAU binds to an adenosine-rich region near the 3-end of the RNA. RHAU truncations support binding that is dependent upon a region within the C terminus and is specific to RHAU isoform 1. Tests performed to assess whether BC200 interferes with RHAU helicase activity have demonstrated the ability of BC200 to act as an acceptor of unwound quadruplexes via a cytosine-rich region near the 3-end of the RNA. Furthermore, an interaction between BC200 and the quadruplex-containing telomerase RNA was confirmed by pull-down assays of the endogenous RNAs. This leads to the possibility that RHAU may direct BC200 to bind and exert regulatory functions at quadruplex-containing RNA or DNA sequences.RNA helicase associated with AU-rich element (RHAU), 8 also known as DHX36 and G4R1, is an ATP-dependent DEAHbox RNA helicase initially characterized as a regulator of mRNA stability via binding to the AU-rich element of urokinase plasminogen activator mRNA (1). Subsequent to this, the discovery that RHAU possesses the ability to unwind both DNA and RNA quadruplexes shifted the focus of RHAU to a role in quadruplex biology (2-4).Quadruplexes are stable secondary structures that occur in guanine-rich nucleic acids through the alignment and hydrogen bonding of guanines in multiple tetrad planes (5). A typical requirement for quadruplex formation is the presence of four tracts of three or more guanines that align in parallel or antiparallel strands with short (Ͻ7-nt) interspersed loops (6); however, quadruplexes with longer loops have also been reported (7,8). Quadruplexes have been shown to possess myriad roles in gene transcription and post-transcriptional regulation of both coding and non-coding RNAs (9 -16).The quadruplex binding specificity of RHAU is mediated by a short N-terminal motif, referred to as the RHAU-specific motif (RSM). In addition to the RSM, RHAU contains a catalytic helicase core (DEXDc and HELICc domains) as well as an HA2 domain and oligosaccharide binding (OB) fold. Whereas the RSM confers quadruplex interacting specificity, maximal quadruplex binding affinity requires the presence of the helicase core (17, 18). The DHX36 gene generates two known splice variants of RHAU. Whereas isoform 1 localizes to both nucleus and cytoplasm, isoform 2 lacks 14 amino acids within the helicase domain and is p...

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“…These tools can estimate G4s with two or three tetrads with the following motif: G x N y 1 G x N y 2 G x N y 3 G x , where ‘ x ’ is the number of guanines ( x > 1) and ‘ y 1 , y 2 , and y 3 , are the lengths of the loops ( y < 37). While this consensus sequence has allowed the identification of many biologically relevant DNA G4s, it might not be appropriate for RNA G4s [38]. RNA molecules being single-stranded, they display a much larger structural diversity than DNA, often involving long-range interactions, and RNA G4s might be embedded within larger structural motifs.…”

Section: Current Methods For Identifying and Characterizing Rna G4smentioning

confidence: 99%

“…( D ) In-line probing of a 54-nucleotide G4 RNA in the presence of either K + or Li + ions (reproduced with permission from ref. [38]).…”

Section: Future Challenges For Investigating Cellular and Functional mentioning

confidence: 99%

Do we know whether potential G-quadruplexes actually form in long functional RNA molecules?

Weldon

Eperon

Dominguez

2016

Biochemical Society Transactions

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The roles of deoxyribonucleic acid (DNA) G-quadruplex structures in gene expression and telomere maintenance have been well characterized. Recent results suggest that such structures could also play pivotal roles in ribonucleic acid (RNA) biology, such as splicing or translation regulation. However, it has been difficult to show that RNA G-quadruplexes (G4s) exist in specific long RNA sequences, such as precursor messenger RNA, in a functional or cellular context. Most current methods for identifying G4s involve the use of short, purified RNA sequences in vitro, in the absence of competition with secondary structures or protein binding. Therefore, novel methods need to be developed to allow the characterization of G4s in long functional RNAs and in a cellular context. This need has in part been met by our recent development of a method based on a comparison of RNA and 7-deaza-RNA that provides a test for identifying RNA G4s in such conditions.

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The folding of 5′-UTR human G-quadruplexes possessing a long central loop

Cited by 58 publications

References 44 publications

RNA G-quadruplexes and their potential regulatory roles in translation

RNA G-quadruplexes and their potential regulatory roles in translation

RNA Helicase Associated with AU-rich Element (RHAU/DHX36) Interacts with the 3′-Tail of the Long Non-coding RNA BC200 (BCYRN1)

Do we know whether potential G-quadruplexes actually form in long functional RNA molecules?

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