Alternative splicing modulation by G-quadruplexes

Soares, Georgakopoulos; Parada, Guillermo E.; Wong, K.F.; Miska, Eric A.; Kwok, Chun Kit; Hemberg,

doi:10.1101/700575

Cited by 8 publications

(3 citation statements)

References 90 publications

(133 reference statements)

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“…Here, from 50–60%, G4s colocalize with transcription factories and nuclear speckles; thus, they appear in proximity to transcription sites that are likely spliced cotranscriptionally ( Figure 5 A,B). This observation is in agreement with Georgakopoulos-Soares et al showing that an appearance of G4s in the sites of the alternative splicing could be one possibility of splicing regulation [ 58 ]. In general, these data document a high density of G4s in GC-rich (euchromatin) sequences.…”

Section: Discussionsupporting

confidence: 92%

G-Quadruplex Structures Colocalize with Transcription Factories and Nuclear Speckles Surrounded by Acetylated and Dimethylated Histones H3

Komůrková

Kovaříková

Bártová

2021

IJMS

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G-quadruplexes (G4s) are four-stranded helical structures that regulate several nuclear processes, including gene expression and telomere maintenance. We observed that G4s are located in GC-rich (euchromatin) regions and outside the fibrillarin-positive compartment of nucleoli. Genomic regions around G4s were preferentially H3K9 acetylated and H3K9 dimethylated, but H3K9me3 rarely decorated G4 structures. We additionally observed the variability in the number of G4s in selected human and mouse cell lines. We found the highest number of G4s in human embryonic stem cells. We observed the highest degree of colocalization between G4s and transcription factories, positive on the phosphorylated form of RNA polymerase II (RNAP II). Similarly, a high colocalization rate was between G4s and nuclear speckles, enriched in pre-mRNA splicing factor SC-35. PML bodies, the replication protein SMD1, and Cajal bodies colocalized with G4s to a lesser extent. Thus, G4 structures seem to appear mainly in nuclear compartments transcribed via RNAP II, and pre-mRNA is spliced via the SC-35 protein. However, α-amanitin, an inhibitor of RNAP II, did not affect colocalization between G4s and transcription factories as well as G4s and SC-35-positive domains. In addition, irradiation by γ-rays did not change a mutual link between G4s and DNA repair proteins (G4s/γH2AX, G4s/53BP1, and G4s/MDC1), accumulated into DNA damage foci. Described characteristics of G4s seem to be the manifestation of pronounced G4s stability that is likely maintained not only via a high-order organization of these structures but also by a specific histone signature, including H3K9me2, responsible for chromatin compaction.

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Section: Discussionsupporting

confidence: 92%

G-Quadruplex Structures Colocalize with Transcription Factories and Nuclear Speckles Surrounded by Acetylated and Dimethylated Histones H3

Komůrková

Kovaříková

Bártová

2021

IJMS

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“…telomeric equilibrium, replication origin, autophagy, polyadenylation, splicing, etc.) [3][4][5][6] . This also explains why G4-involving cellular events are now being actively investigated as targets for chemotherapeutic interventions, according to an innovative strategy relying on the use of nucleic acid structure-specific binders 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Small molecule chaperones facilitate the folding of long non-coding RNA G

Lejault

Prudent

Terrier

et al. 2023

Preprint

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RNA G-quadruplexes (rG4) have recently emerged as major regulatory elements in both mRNA 21 and non-coding RNA. To investigate the biological roles of the rG4 structures, chemists have 22 developed a variety of highly specific and potent ligands. All these ligands bind to the rG4 by 23 staking on their top, and the specificity of binding is demonstrated in comparison to other 24 structures such as duplex or three-way junctions. It remains unclear whether rG4-ligands 25 merely stabilize fully formed rG4 structures, or if they actively participate in the folding of the 26 rG4 structure through their association with an unfolded RNA sequence. In order to access 27 the innate steps of ligand-rG4 association and mechanisms, robust in vitro techniques, 28 including FRET, electrophoretic mobility shift assay and reverse transcriptase stalling assays, 29 were used to examine the capacity of five well-known G4 ligands to induce rG4 structures 30 derived from either long non-coding RNAs of from synthetic RNAs. It was found that both 31 PhenDC3 and PDS induce rG4 formation in unfolded single RNA strands. This discovery has 32 important implications for the interpretation of RNA-seq experiments. Overall, in vitro data 33 that can assist biochemists in selecting the optimal G4-ligands for their RNA cellular 34 experiments are presented, while also considering the effects induced by these ligands of the 35 rG4.

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“…Some of these G4 motifs are involved in DNA replication, recombination, telomere regulation and transcriptional regulation ( Figure 1 ) ( Métifiot et al, 2014 ; Yang, 2019 ; Prorok et al, 2019 ; Cammas and Millevoi, 2017 ). Some G4 motifs are copied into RNAs, thereby leading to the regulation of RNA functions such as processing, stability, translation and transport ( Figure 1 ) ( Bugaut and Balasubramanian, 2012 ; Cammas and Millevoi, 2017 ; Yang, 2019 ; Shao et al, 2020 ; Dumas et al, 2021 ; Georgakopoulos-Soares et al, 2022 ). G4-RNAs are often assembled into unique ribonucleoprotein (RNP) granules without boundary membranes, which were identified as precipitats in the brain tissue and cultured cell extracts using biotinylated isoxazole ( Subramanian et al, 2011 ; Han et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Essential Roles and Risks of G-Quadruplex Regulation: Recognition Targets of ALS-Linked TDP-43 and FUS

Ishiguro

Ishihama

2022

Front. Mol. Biosci.

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A non-canonical DNA/RNA structure, G-quadruplex (G4), is a unique structure formed by two or more guanine quartets, which associate through Hoogsteen hydrogen bonding leading to form a square planar arrangement. A set of RNA-binding proteins specifically recognize G4 structures and play certain unique physiological roles. These G4-binding proteins form ribonucleoprotein (RNP) through a physicochemical phenomenon called liquid-liquid phase separation (LLPS). G4-containing RNP granules are identified in both prokaryotes and eukaryotes, but extensive studies have been performed in eukaryotes. We have been involved in analyses of the roles of G4-containing RNAs recognized by two G4-RNA-binding proteins, TDP-43 and FUS, which both are the amyotrophic lateral sclerosis (ALS) causative gene products. These RNA-binding proteins play the essential roles in both G4 recognition and LLPS, but they also carry the risk of agglutination. The biological significance of G4-binding proteins is controlled through unique 3D structure of G4, of which the risk of conformational stability is influenced by environmental conditions such as monovalent metals and guanine oxidation.

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Alternative splicing modulation by G-quadruplexes

Cited by 8 publications

References 90 publications

G-Quadruplex Structures Colocalize with Transcription Factories and Nuclear Speckles Surrounded by Acetylated and Dimethylated Histones H3

G-Quadruplex Structures Colocalize with Transcription Factories and Nuclear Speckles Surrounded by Acetylated and Dimethylated Histones H3

Small molecule chaperones facilitate the folding of long non-coding RNA G

Essential Roles and Risks of G-Quadruplex Regulation: Recognition Targets of ALS-Linked TDP-43 and FUS

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