Impairment of pre-mRNA splicing in liver disease: mechanisms and consequences

Pre-mRNA splicing is an essential step in the process of gene expression in eukaryotes and consists of the removal of introns and the linking of exons to generate mature mRNAs. This is a highly regulated mechanism that allows the alternative usage of exons, the retention of intronic sequences and th...

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Detalles Bibliográficos
Autores: Berasain-Lasarte, C. (Carmen)|||/items/f1d61c19-1753-4442-a3fd-cc90220e84a0, Goñi, S. (Saioa)|||/items/30c9118a-59e0-41e1-9d9a-a41414437869, Castillo, J. (Josefa)|||/items/1a0bbe63-5946-4bcb-b5b4-1041fd6966a2, Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356, Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71, Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f
Tipo de recurso: artículo
Fecha de publicación:2010
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/57783
Acceso en línea:https://hdl.handle.net/10171/57783
Access Level:acceso abierto
Palabra clave:Cell signalling
Hepatocarcinogenesis
Pre- mRNA splicing
Splicing factors
Targeted anticancer therapy
Descripción
Sumario:Pre-mRNA splicing is an essential step in the process of gene expression in eukaryotes and consists of the removal of introns and the linking of exons to generate mature mRNAs. This is a highly regulated mechanism that allows the alternative usage of exons, the retention of intronic sequences and the generation of exonic se- quences of variable length. Most human genes undergo splicing events, and disruptions of this process have been associated with a variety of diseases, including cancer. Hepatocellular carcinoma (HCC) is a molecularly heterogeneous type of tumor that usually develops in a cirrhotic liver. Alterations in pre-mRNA splicing of some genes have been observed in liver cancer, and although still scarce, the available data suggest that splicing de- fects may have a role in hepatocarcinogenesis. Here we briefly review the general mechanisms that regulate pre-mRNA splicing, and discuss some examples that illustrate how this process is impaired in liver tumori- genesis, and may contribute to HCC development. We believe that a more thorough examination of pre-mRNA splicing is still needed to accurately draw the molecular portrait of liver cancer. This will surely contribute to a better understanding of the disease and to the develop- ment of new effective therapies.