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LLPS de FXR1 impulsa la espermiogénesis mediante la activación de la traducción de los ARNm almacenados

Jun-Yan Kang¹, Ze Wen¹, Duo Pan¹

¹State Key Laboratory of Molecular Biology, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

Science (New York, N.Y.)

|August 11, 2022

Resumen

La proteína frágil relacionada con X (FXR) 1 impulsa la activación génica en el desarrollo de los espermatozoides. Esta proteína de unión al ARN utiliza la separación de fase líquido-líquido para activar los ARN mensajeros almacenados, asegurando la formación adecuada de espermatozoides y la fertilidad masculina.

Área de la Ciencia:

Biología molecular
Biología de la reproducción
Biología celular

Sus antecedentes:

Los espermatidos posmeióticos coordinan la expresión génica con cambios morfológicos.
El ARNm se almacena en gránulos de ribonucleoproteína mensajera traslacionalmente inertes durante el desarrollo de los espermatozoides.
Se desconocen en gran medida los mecanismos para activar los ARNm almacenados en los espermatozoides.

Objetivo del estudio:

Investigar el papel de la proteína de unión al ARN Fragile X-related (FXR) 1 en el desarrollo de los espermatozoides.
Elucidar el mecanismo por el cual los ARNm almacenados se activan por traducción en espermatidas tardías.
Determinar la participación de la separación de fase líquido-líquido (LLPS) en este proceso.

Principales métodos:

Investigó la expresión y la función de FXR1 en espermatidas tardías.
Se utilizó la ablación específica de la línea germinal Fxr1 en ratones.
Se generaron ratones knock-in Fxr1 con una mutación de deficiencia de separación de fase (FXR1 L351P).
Se analizó la traducción del ARNm y el desarrollo de los espermatozoides.

Principales resultados:

FXR1 se expresa en gran medida en los espermatidos tardíos y media la activación traslacional de los ARNm almacenados a través del LLPS.
La ablación específica de la línea germinal Fxr1 conduce a una traducción alterada del ARNm, un desarrollo defectuoso de los espermatozoides y infertilidad masculina.
Una mutación de FXR1 con deficiencia de separación de fase recapitula estos defectos de desarrollo.

Conclusiones:

FXR1 utiliza LLPS para fusionar gránulos de ribonucleoproteína mensajera con la maquinaria de traducción, activando los ARNm almacenados.
Este mecanismo LLPS impulsado por FXR1 es crucial para la reprogramación traslacional durante la espermiogénesis.
El LLPS mediado por FXR1 es esencial para el desarrollo normal de los espermatozoides y la fertilidad masculina.

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