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El agrupamiento de nucleobases contribuye a la formación y el vaciado del condensado de ARN de expansión repetida
Yingxue Ma1, Haozheng Li2, Zhou Gong1
1CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, National Center for Magnetic Resonance at Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.
Journal of the American Chemical Society
|February 18, 2022
Resumen
Las moléculas de ARN con expansiones repetidas forman gotas parecidas a gel, que pueden causar enfermedades neurodegenerativas. Estas gotas muestran nucleobases agrupadas y se endurecen con el tiempo, impactando en los orgánulos que contienen ARN.
Área de la Ciencia:
- La bioquímica
- Biología molecular
- La neurociencia
Sus antecedentes:
- Las secuencias de expansión repetidas en el ARN pueden conducir a la separación de fase y la formación de condensados parecidos a un gel.
- Esta separación de fases está relacionada con la patogénesis de las enfermedades neurodegenerativas.
Objetivo del estudio:
- Investigar el autoensamblaje de moléculas de ARN con secuencias de expansión repetidas en presencia de Mg2+.
- Caracterizar los cambios morfológicos y estructurales durante la separación de fase del ARN.
Principales métodos:
- Utilizando microscopía Raman hiperespectral estimulada para analizar la formación y estructura de gotas de ARN.
- Investigar el efecto de la variación de la relación ARN/Mg2+ en la morfología de las gotas.
Principales resultados:
- Las moléculas de ARN con 20× repeticiones de CAG se autoensamblan en tres tipos de gotas distintas en presencia de Mg2+.
- La separación de fase de ARN implica el agrupamiento de bases nucleares y la pérdida del emparejamiento de bases canónicas.
- La morfología de las gotas pasa de la expansión a las vesículas huecas con un aumento de la relación ARN/Mg2+.
- El agrupamiento de nucleobases se concentra en el borde de la gota, lo que indica un proceso de endurecimiento.
Conclusiones:
- La separación de fase del ARN impulsada por expansiones repetidas y cationes divalentes puede formar estructuras distintas.
- El mecanismo de endurecimiento observado en el borde de la gota puede ser relevante para el envejecimiento de los orgánulos que contienen ARN.
- Este estudio proporciona información sobre los mecanismos físicos subyacentes a la formación de condensados de ARN y su posible papel en las enfermedades y el envejecimiento.
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