RESUMO
MicroRNA (miRNA) are short non-coding RNA molecules that regulate multiple cellular processes, including development, cell differentiation, proliferation and death. Nevertheless, little is known on whether miRNA control the same gene networks in different tissues. miR-709 is an abundant miRNA expressed ubiquitously. Through transcriptome analysis, we have identified targets of miR-709 in hepatocytes. miR-709 represses genes implicated in cytoskeleton organization, extracellular matrix attachment, and fatty acid metabolism. Remarkably, none of the previously identified targets in non-hepatic tissues are silenced by miR-709 in hepatocytes, even though several of these genes are abundantly expressed in liver. In addition, miR-709 is upregulated in hepatocellular carcinoma, suggesting it participates in the genetic reprogramming that takes place during cell division, when cytoskeleton remodeling requires substantial changes in gene expression. In summary, the present study shows that miR-709 does not repress the same pool of genes in separate cell types. These results underscore the need for validating gene targets in every tissue a miRNA is expressed.
Assuntos
Carcinoma Hepatocelular/genética , Redes Reguladoras de Genes , Hepatócitos/metabolismo , Neoplasias Hepáticas/genética , MicroRNAs/genética , Transcriptoma , Animais , Sequência de Bases , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genes Reporter , Hepatócitos/citologia , Humanos , Metabolismo dos Lipídeos/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Luciferases/genética , Luciferases/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Especificidade de Órgãos , Cultura Primária de Células , TransfecçãoRESUMO
When hybrid inviability is an indirect by-product of local adaptation, we expect its degree of severity between pairs of populations to vary and to be sensitive to the environment. While complete reciprocal hybrid inviability is the outcome of the gradual process of local adaptation, it is not representative of the process of accumulation of incompatibility. In the flour beetle, Tribolium castaneum, some pairs of populations exhibit complete, reciprocal F1 hybrid incompatibility while other pairs are fully or partially compatible. We characterize this naturally occurring variation in the degree and timing of expression of the hybrid incompatible phenotype to better understand the number of genes or developmental processes contributing to speciation. We assessed the morphological and developmental variation in four Tribolium castaneum populations and their 12 possible F1 hybrids at each life-history stage from egg to adult. We find that the rate of hybrid larval development is affected in all interpopulation crosses, including those eventually producing viable, fertile adults. Hybrid incompatibility manifests early in development as changes in the duration of instars and diminished success in the transition between instars are relative to the parent populations. Parent populations with similar developmental profiles may produce hybrids with disrupted development. The degree and timing of expression of hybrid inviability depends upon populations crossed, direction of the cross, and environment in which hybrids are raised. Our findings suggest that the coordinated expression of genes involved in transitional periods of development is the underlying cause of hybrid incompatibility in this species.