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Peer-reviewedCC BY 4.0Biomolecules

G-Quadruplexes at the ‘Interface’ of Transcription and Alternative Splicing

  • Pavel Rubtsov1
  • Julia Khomyakova1
  • Anna Varizhuk1
  1. 1Cellular Biology Department, Federal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, Russia
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Abstract

DNA and RNA G-quadruplexes (G4s and rG4s, respectively) are well-known modulators of transcription and splicing. G4s are enriched in transcriptionally active chromatin domains that produce transcripts susceptible to alternative splicing (AS), at least in higher vertebrates. These domains are arranged close to nuclear speckles (NSs), where key AS regulators are stored. Recent findings have revealed new aspects of cotranscriptional AS, emphasizing the advantages of transient rG4s and revealing the connection between excessive rG4s and disease. Here, we discuss how (r)G4s’ presumed ability to promote liquid–liquid phase separation at active chromatin and their affinity for dual regulators of transcription and splicing has brought them to the forefront of communication between NSs and their associated chromatin domains. We also discuss how NS components may contribute to maintaining balanced (r)G4 folding, provide examples of imbalance, and analyze the prospects of G4-based AS reprogramming.

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Cite

BibTeXRIS
BibTeX
@article{rubtsov2026gquadruplexes,
  title = {{G-Quadruplexes at the ‘Interface’ of Transcription and Alternative Splicing}},
  author = {Pavel Rubtsov and Julia Khomyakova and Anna Varizhuk},
  journal = {Biomolecules},
  year = {2026},
  month = oct,
  doi = {10.3390/biom16111554},
  url = {https://www.mdpi.com/2218-273X/16/11/1554},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - G-Quadruplexes at the ‘Interface’ of Transcription and Alternative Splicing
AU  - Pavel Rubtsov
AU  - Julia Khomyakova
AU  - Anna Varizhuk
PY  - 2026
DA  - 2026/10/24
JO  - Biomolecules
DO  - 10.3390/biom16111554
UR  - https://www.mdpi.com/2218-273X/16/11/1554
AB  - DNA and RNA G-quadruplexes (G4s and rG4s, respectively) are well-known modulators of transcription and splicing. G4s are enriched in transcriptionally active chromatin domains that produce transcripts susceptible to alternative splicing (AS), at least in higher vertebrates. These domains are arranged close to nuclear speckles (NSs), where key AS regulators are stored. Recent findings have revealed new aspects of cotranscriptional AS, emphasizing the advantages of transient rG4s and revealing the connection between excessive rG4s and disease. Here, we discuss how (r)G4s’ presumed ability to promote liquid–liquid phase separation at active chromatin and their affinity for dual regulators of transcription and splicing has brought them to the forefront of communication between NSs and their associated chromatin domains. We also discuss how NS components may contribute to maintaining balanced (r)G4 folding, provide examples of imbalance, and analyze the prospects of G4-based AS reprogramming.
SN  - 2218-273X
ER  -