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Los intrones lineales extirpados regulan el crecimiento de la levadura

Jeffrey T Morgan^1,2,3, Gerald R Fink^2,3, David P Bartel^4,5,6

¹Howard Hughes Medical Institute, Cambridge, MA, USA.

|January 18, 2019

Resumen

Los intrones cortados en la levadura se estabilizan bajo estrés, funcionando dentro de la red de señalización de crecimiento TOR. Estos intrones específicos, cuando se eliminan, causan un crecimiento aberrante, destacando su importancia biológica.

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Área de la Ciencia:

Biología molecular
Genética de la levadura
Biología del ARN

Sus antecedentes:

Los intrones espliceosomales son ARN no codificantes que generalmente se degradan rápidamente después de la escisión.
El objetivo del complejo de rapamicina 1 (TORC1) es un regulador central del crecimiento celular y el metabolismo.

Objetivo del estudio:

Investigar el destino y la función de los intrones extirpados en Saccharomyces cerevisiae bajo condiciones de estrés.
Identificar los mecanismos moleculares que rigen la estabilización de intrones y su papel en la señalización celular.

Principales métodos:

Análisis de la acumulación de intrones extirpados en levaduras bajo crecimiento saturado e inhibición de TORC1.
Caracterización de la asociación de los intrones estabilizados con los componentes espliceosomales.
Manipulación genética (eliminación y reintroducción) de intrones específicos para evaluar su impacto en el crecimiento de la levadura y la respuesta al estrés.

Principales resultados:

Un subconjunto de 34 intrones extirpados se acumula como ARN lineales bajo inhibición de TORC1 o crecimiento saturado.
Los intrones estabilizados poseen una corta distancia entre el punto de ramificación lariat y el sitio de empalme de 3 ', crucial para su estabilidad.
La eliminación de estos intrones perjudica la aptitud de la levadura en condiciones saturadas y conduce a un crecimiento aberrante bajo tratamiento con rapamicina.

Conclusiones:

Los intrones extirpados pueden estabilizarse bajo condiciones de estrés específicas, revelando una función biológica no reconocida anteriormente.
Estos intrones estabilizados juegan un papel en la red de señalización de crecimiento TORC1 en S. cerevisiae.
Los hallazgos sugieren que los intrones espliceosómicos extirpados tienen funciones biológicas más amplias que su papel en el empalme pre-ARNm.