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El control del empalme de ARN alternativo y la expresión génica por medio de riboswitches eucariotas

Ming T Cheah¹, Andreas Wachter, Narasimhan Sudarsan

¹Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.

|May 1, 2007

Resumen

Las células eucariotas utilizan ARN de unión al metabolito llamados riboswitches para controlar la expresión génica. En los hongos, los riboswitches de tiamina pirofosfato (TPP) regulan el empalme del ARN mensajero, lo que afecta el metabolismo del TPP.

Área de la Ciencia:

Biología Molecular Biología Molecular
La bioquímica es la bioquímica.
Regulación del gen de los eucariotas.

Sus antecedentes:

Las bacterias utilizan riboswitches para detectar metabolitos y regular la expresión génica, principalmente a través de la terminación de la transcripción o el inicio de la traducción.
El riboswitch de tiamina pirofosfato (TPP), que responde a un derivado de la vitamina B1, está muy extendido en las bacterias y se predice que controla el procesamiento del ARN en los eucariotas.
Se supone que los riboswitches TPP eucariotas influyen en el empalme o procesamiento del ARN mensajero (ARNm).

Objetivo del estudio:

Para investigar la función de los riboswitches TPP en el hongo filamentoso Neurospora crassa.
Para determinar cómo los riboswitches TPP regulan la expresión génica en el nivel de empalme de ARNm en eucariotas.
Para dilucidar el mecanismo de control de empalme alternativo mediado por riboswitch en el metabolismo de TPP.

Principales métodos:

Análisis de tres riboswitches TPP en Neurospora crassa.
Examen experimental de la regulación de la expresión génica.
Estudio mecanicista detallado de los cambios de emparejamiento de bases mediados por riboswitch y el empalme alternativo para los ARNm precursores de NMT1.

Principales resultados:

Se descubrió que un riboswitch TPP activaba la expresión génica, mientras que dos la reprimían, todo controlando el empalme del ARNm.
Se aclaró un mecanismo específico para los ARNm NMT1 precursores, lo que demuestra el control del riboswitch sobre el empalme alternativo.
Estos hallazgos resaltan el papel de los riboswitches de TPP en la regulación de los genes involucrados en el metabolismo de TPP a través de la modulación de empalme.

Conclusiones:

Las células eucariotas emplean ARN sensores de metabolitos (riboswitches) para regular el empalme de ARN.
Los riboswitches TPP en los hongos controlan la expresión génica mediante la modulación del empalme de ARNm alternativo.
Este mecanismo es crucial para regular los procesos bioquímicos clave, como el metabolismo de la TPP, en los organismos eucariotas.

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