Can loss-of-function prion-related diseases exist?

Discovery of mutations of the PrnP gene without typical plaque formation and the characterization of two prion receptors led us to postulate a new class of prion-related disease: 'loss of function'.Ludwig Inst Canc Res, BR-01509010 São Paulo, BrazilUNIFESP, Dept Psychiat, BR-01509010 São Paulo, BrazilUNIFESP, Dept Psychiat, BR-01509010 São Paulo, BrazilWeb of Scienc

Long-Range Heterogeneity at the 3′ Ends of Human mRNAs

The publication of a draft of the human genome and of large collections of transcribed sequences has made it possible to study the complex relationship between the transcriptome and the genome. In the work presented here, we have focused on mapping mRNA 3′ ends onto the genome by use of the raw data generated by the expressed sequence tag (EST) sequencing projects. We find that at least half of the human genes encode multiple transcripts whose polyadenylation is driven by multiple signals. The corresponding transcript 3′ ends are spread over distances in the kilobase range. This finding has profound implications for our understanding of gene expression regulation and of the diversity of human transcripts, for the design of cDNA microarray probes, and for the interpretation of gene expression profiling experiments. [The following individuals kindly provided reagents, samples or unpublished information as indicated in the paper: G. Riggins, C. Ruegg, J.-B. Demoulin, P. Olsson, F. Funari, P. Schneider, L.F. Reis, and J.-C. Renauld