RESUMEN
Nonsense-mediated decay is well known by the lucid definition of being a RNA surveillance mechanism that ensures the speedy degradation of mRNAs containing premature translation termination codons. However, as we review here, NMD is far from being a simple quality control mechanism; it also regulates the stability of many wild-type transcripts. We summarise the abundance of research that has characterised each of the NMD factors and present a unified model for the recognition of NMD substrates. The contentious issue of how and where NMD occurs is also discussed, particularly with regard to P-bodies and SMG6-driven endonucleolytic degradation. In recent years, the discovery of additional functions played by several of the NMD factors has further complicated the picture. Therefore, we also review the reported roles of UPF1, SMG1 and SMG6 in other cellular processes.
Asunto(s)
Células/metabolismo , Codón sin Sentido/metabolismo , Procesamiento Postranscripcional del ARN/fisiología , Estabilidad del ARN/genética , Factores de Transcripción/fisiología , Fenómenos Biomecánicos , Enfermedad/etiología , Enfermedad/genética , Humanos , Modelos Biológicos , Control de Calidad , Estabilidad del ARN/fisiología , Transactivadores/genética , Transactivadores/metabolismo , Transactivadores/fisiología , Factores de Transcripción/metabolismoRESUMEN
Among the different cellular surveillance mechanisms in charge to prevent production of faulty gene products, nonsense-mediated mRNA decay (NMD) represents a translation-dependent posttranscriptional process that selectively recognizes and degrades mRNAs whose open reading frame (ORF) is truncated by a premature translation termination codon (PTC, also called "nonsense codon"). In doing so, NMD protects the cell from accumulating C-terminally truncated proteins with potentially deleterious functions. Transcriptome profiling of NMD-deficient yeast, Drosophila, and human cells revealed that 3-10% of all mRNA levels are regulated (directly or indirectly) by NMD, indicating an important role of NMD in gene regulation that extends beyond quality control [J. Rehwinkel, J. Raes, E. Izaurralde, Nonsense-mediated mRNA decay: Target genes and functional diversification of effectors, Trends Biochem. Sci. 31 (2006) 639-646.[1]]. In this review, we focus on recent results from different model organisms that indicate an evolutionarily conserved mechanism for PTC identification.
