Referencia

Mol Cell. 2014 Jun 4. pii: S1097-2765(14)00399-2. doi: 10.1016/j.molcel.2014.05.005.

Autores

Liz J, Portela A, Soler M, Gómez A, Ling H, Michlewski G, Calin GA, Guil S, Esteller M.

Resumen

Noncoding RNAs (ncRNAs) control cellular programs by affecting protein-coding genes, but evidence increasingly points to their involvement in a network of ncRNA-ncRNA interactions. Here, we show that a long ncRNA, Uc.283+A, controls pri-miRNA processing. Regulation requires complementarity between the lower stem region of the pri-miR-195 transcript and an ultraconserved sequence in Uc.283+A, which prevents pri-miRNA cleavage by Drosha. Mutation of the site in either RNA molecule uncouples regulation in vivo and in vitro. We propose a model in which lower-stem strand invasion by Uc.283+A impairs microprocessor recognition and efficient pri-miRNA cropping. In addition to identifying a case of RNA-directed regulation of miRNA biogenesis, our study reveals regulatory networks involving different ncRNA classes of importance in cancer.

Descripción

La biogenesis de microARNs es un proceso que incluye múltiples pasos que regulan de una manera muy ajustada la cantidad final de un microARN maduro funcional. El presente trabajo describe la caracterización funcional de un ARN no codificante largo transcrito desde una zona ultraconservada del genoma, T-UCR. Este T-UCR, inhibe el correcto procesamiento de un pri-microRNA por parte del Microprocesador a través de una interacción ARN:ARN que implica a la zona ultraconservada del T-UCR con la zona del pri-microARN clave para el reconocimiento por parte de DGCR8 y la posterior catálisis por parte de DROSHA.

grupo

REFERENCIA DEL GRUPO INVESTIGADOR

El grupo del Dr. Esteller presenta como mayor objetivo esclarecer los mecanismos epigenéticos que subyacen en el desarrollo y progresión del cáncer. El cáncer, desde un punto de vista epigenético, está caracterizado por la disrupción de los patrones de metilación del DNA, RNAs no codificantes y las modificaciones de histonas. La interrelación entre estos tres factores epigenéticos es clave para la correcta regulación de la expresión génica.

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