RNA interference: a novel and physiologic mechanism of gene silencing with great therapeutic potential

The post-genomics scientific era has evolved rapidly while achieving advanced understanding of the structure and function of the genes responsible for both the phenotypic characteristics of higher organisms and the pathophysiology of several genetic diseases. Researchers in the fields of oncology and infectious diseases have become more convinced of the great potential of molecular biology approaches to further develop highly specific diagnostic and less toxic therapeutic strategies. During the last two decades, approaches for the specific silencing of essential viral genes and cellular oncogenes were evaluated with optimism for developing directed therapies. However, there were drawbacks in the use of antisense oligonucleotides as a practical mechanism of achieving gene silencing both in vitro and in vivo. Recently, a novel role for post-transcriptional gene silencing mediated by double-stranded RNA (dsRNA) was discovered in the experimental model of C. elegans. This mechanism, termed RNA interference (RNAi) has also been found in other eukaryotes, from plants to mammals, including humans. RNAi is presently being explored both in vitro and in vivo in functional genomics studies and possible therapeutic uses due to its highly specific and physiologic mode of gene silencing. This article focuses on the most current information available regarding the RNAi mechanism and its uses in models of cancer and infectious diseases.

Protein synthesis in eukaryotes: The growing biological relevance of cap-independent translation initiation

Ribosome recruitment to eukaryotic mRNAs is generally thought to occur by a scanning mechanism, whereby the 40S ribosomal subunit binds in the vicinity of the 5'cap structure of the mRNA and scans until an AUG codon is encountered in an appropriate sequence context. Study of the picornaviruses allowed the characterization of an alternative mechanism of translation initiation. Picornaviruses can initiate translation via an internal ribosome entry segment (IRES), an RNA structure that directly recruits the 40S ribosomal subunits in a cap and 5' end independent fashion. Since its discovery, the notion of IRESs has extended to a number of different virus families and cellular RNAs. This review summarizes features of both cap-dependent and IRES-dependent mechanisms of translation initiation and discusses the role of cis-acting elements, which include the 5'cap, the 5'-untranslated region (UTR) and the poly(A) tail as well as the possible roles of IRESs as part of a cellular stress response mechanism and in the virus replication cycle.

Síndrome de disfunción (falla) orgánica múltiple en pediatría / Multisystem organ dysfunction (failure) syndrome in childhood

El síndrome de disfunción (falla) orgánica múltiple es diagnosticado cada vez con más frecuencia en todo el espectro etario. La sobrevida lograda con los avances en las técnicas de resucitación de shock, sepsis y trauma se ha visto acompañada de una mayor incidencia de esta entidad. A pesar de casi una década de su descripción en niños y de su importancia existen muy pocas publicaciones en pediatría. Inicialmente se pensaba que el síndrome era sinónimo de complicaciones infecciosas y/o trauma. La caracterización de esta enfermedad, la importancia del "huésped" en la fisiopatología y manifestaciones clínicas del síndrome, el cuadro clínico, los principios terapéuticos, la prevención y su pronóstico son analizados en detalle en una revisión extensa de la literatura