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.

Descárgate este artículo aquí.
Más artículos en la revista SEBBM.

¿Acabas de publicar un artículo interesante?

Manda la referencia a través de nuestro formulario.  Límite de edad 32 años. Los artículos seleccionados serán destacados como artículos del mes y participarán en el Premio Fisher Scientific, que se entregará en el congreso de la SEBBM (inscripción y alojamiento gratuitos).

Otros "Artículos del mes"

Crebbp loss cooperates with Bcl2 overexpression to promote lymphoma in mice.

01-07-2017

CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits...

Leer más

Local amplifiers of IL-4Rα-mediated macrophage activation promote repair in lung and liver

01-06-2017

The type 2 immune response controls helminth infection and maintains tissue homeostasis but can lead to allergy and fibrosis if not adequately regulated. We have discovered local tissue-specific amplifiers of...

Leer más

Programmed mitophagy is essential for the glycolytic switch during cell differentiation

01-05-2017

Retinal ganglion cells (RGCs) are the sole projecting neurons of the retina and their axons form the optic nerve. Here, we show that embryogenesis-associated mouse RGC differentiation depends on mitophagy...

Leer más

Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes

01-04-2017

The Bcl-2 (B-cell lymphoma 2) protein Bax (Bcl-2 associated X, apoptosis regulator) can commit cells to apoptosis via outer mitochondrial membrane permeabilization. Bax activity is controlled in healthy cells by...

Leer más

Histone chaperone activity of Arabidopsis thaliana NRP1 is blocked by cytochrome c

01-03-2017

Higher-order plants and mammals use similar mechanisms to repair and tolerate oxidative DNA damage. Most studies on the DNA repair process have focused on yeast and mammals, in which histone...

Leer más

The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes

01-02-2017

The thermogenic activity of brown adipose tissue (BAT) and browning of white adipose tissue are important components of energy expenditure. Here we show that GPR120, a receptor for polyunsaturated fatty...

Leer más

Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes

01-01-2017

Neurons depend on oxidative phosphorylation for energy generation, whereas astrocytes do not, a distinctive feature that is essential for neurotransmission and neuronal survival. However, any link between these metabolic differences...

Leer más

A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection

01-12-2016

There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining and homologous recombination. Here we identify and characterize novel factors involved in choosing between these pathways;...

Leer más

In vivo conditional deletion of HDAC7 reveals its requirement to establish proper B lymphocyte identity and development

01-11-2016

Class IIa Histone Deacetylases (HDACs) subfamily members are tissue-specific gene repressors with crucial roles in development and differentiation processes. A prominent example is HDAC7, a class IIa HDAC that shows...

Leer más

DNA demethylation of inflammasome-associated genes is enhanced in patients with cryopyrin-associated periodic syndromes

01-10-2016

Inflammasomes are cytosolic multiprotein complexes in macrophages. They assemble after infection- or stress-associated stimuli, activating both caspase-1-mediated inflammatory cytokine secretion and pyroptosis. Increased inflammasome activity resulting from gene mutations is...

Leer más

Socios Protectores