Las proteínas SMAD controlan la maduración del microARN mediado por DROSHA
Brandi N Davis1, Aaron C Hilyard, Giorgio Lagna
1Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Nature
|June 13, 2008
Resumen
La señalización del factor de crecimiento transformador beta (TGF-beta) y la proteína morfogénica ósea (BMP) aumentan rápidamente los niveles de microRNA-21 (miR-21). Esto mejora la contracción de las células musculares lisas vasculares mediante la desregulación de PDCD4, un regulador negativo de los genes contráctiles.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Los microARN (miRNA) regulan la expresión génica, pero el control de su biogénesis es poco conocido.
- Las vías de señalización del factor de crecimiento transformador beta (TGF-beta) y la proteína morfogénica ósea (BMP) son cruciales para el desarrollo vascular y la homeostasis.
- La expresión desregulada de miRNA está relacionada con enfermedades como el cáncer y los trastornos cardiovasculares.
Objetivo del estudio:
- Investigar el papel de los microARN en el fenotipo de células de músculo liso vascular inducido por TGF-beta y BMP.
- Para dilucidar el mecanismo por el cual la señalización de TGF-beta y BMP regula la biogénesis del miRNA.
Principales métodos:
- PCR cuantitativa en tiempo real para medir el miARN y la expresión génica.
- Western blotting para evaluar los niveles de proteínas.
- Pruebas de inmunoprecipitación para estudiar las interacciones proteína-ARN.
Principales resultados:
- La señalización de TGF-beta y BMP induce la contracción de las células del músculo liso vascular a través de miR-21.
- miR-21 desregula directamente la PDCD4, un represor de los genes contráctiles del músculo liso.
- La señalización de TGF-beta y BMP mejora la producción madura de miR-21 a través del procesamiento post-transcripcional de pri-miR-21 por el complejo DROSHA.
- Las proteínas SMAD y p68/DDX5 son reclutadas en pri-miR-21, lo que facilita el procesamiento de una manera independiente de SMAD4.
Conclusiones:
- La señalización de TGF-beta y BMP regula el fenotipo de las células musculares lisas vasculares a través de miR-21.
- Las proteínas SMAD específicas de los ligandos controlan la biogénesis del miRNA a nivel post-transcripcional.
- Este mecanismo pone de relieve una vía reguladora independiente de SMAD4 en la señalización de TGF-beta y BMP.
Videos de Conceptos Relacionados
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
02:30siRNA - Small Interfering RNAs
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
02:57piRNA - Piwi-interacting RNAs
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
02:15Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...