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Updated: Jan 13, 2026

Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes

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Especificidad de la interacción estabilizadora entre secuencias de proteínas intrínsecamente desordenadas y

Lachlan B Cox^1,2, John S Mattick^2,3, Isis A Middleton^1,2

¹School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia.

Nucleic acids research

|January 7, 2026

Resumen

Las regiones intrínsecamente desordenadas (IDR) estabilizan selectivamente los G-cuádruplexes de ARN (rG4) a través de interacciones débiles. Este mecanismo de plegamiento de ARN explica interacciones específicas y mutaciones en las IDR.

Área de la Ciencia:

Bioquímica; Biología Molecular; Genética

Sus antecedentes:

Las regiones intrínsecamente desordenadas (IDR) son cruciales para la regulación de proteínas y los procesos celulares.; El dominio RGG dentro de las IDR interactúa con los G-cuádruplexes de ARN (rG4), estructuras clave de ARN reguladoras.

Objetivo del estudio:

Investigar el mecanismo por el cual las IDR se unen y estabilizan selectivamente las estructuras rG4.; Elucidar cómo las IDR logran la especificidad en las interacciones rG4.

Principales métodos:

Se utilizaron interacciones de unión débiles entre péptidos ricos en RGG y rG4.; Se empleó RMN multidimensional y espectroscopía de dicroísmo circular (CD).

Principales resultados:

Se demostró que las IDR templan y estabilizan selectivamente la TERRA rG4 humana.; Se mostró que identidades nucleotídicas y de aminoácidos específicas dictan la especificidad de la interacción péptido RGG-rG4.; Se identificó una nueva vía de plegamiento de ARN independiente de la unión de alta afinidad o cationes monovalentes.

Conclusiones:

Las IDR pueden reconocer selectivamente G4 de ARN sobre G4 de ADN debido a determinantes de secuencia específicos.; Los hallazgos explican la alta especificidad de las interacciones IDR-rG4 in vivo y la prevalencia de mutaciones monogénicas en las IDR.

Palabras clave:

proteínas intrínsecamente desordenadas ARN G-cuádruplex interacciones débiles plegamiento de ARN especificidad de unión

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