Assembly defects of human tRNA splicing endonuclease contribute to impaired pre-tRNA processing in pontocerebellar hypoplasia

Mutations within subunits of the tRNA splicing endonuclease complex (TSEN) are associated with pontocerebellar hypoplasia (PCH). Here the authors show that tRNA intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers, and provide evidence that modulation of TSEN stability may contribute to PCH phenotypes.Introns of human transfer RNA precursors (pre-tRNAs) are excised by the tRNA splicing endonuclease TSEN in complex with the RNA kinase CLP1. Mutations in TSEN/CLP1 occur in patients with pontocerebellar hypoplasia (PCH), however, their role in the disease is unclear. Here, we show that intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers independently of CLP1. Splice site recognition involves the mature domain and the anticodon-intron base pair of pre-tRNAs. The 2.1-angstrom resolution X-ray crystal structure of a TSEN15-34 heterodimer and differential scanning fluorimetry analyses show that PCH mutations cause thermal destabilization. While endonuclease activity in recombinant mutant TSEN is unaltered, we observe assembly defects and reduced pre-tRNA cleavage activity resulting in an imbalanced pre-tRNA pool in PCH patient-derived fibroblasts. Our work defines the molecular principles of intron excision in humans and provides evidence that modulation of TSEN stability may contribute to PCH phenotypes.Genetics of disease, diagnosis and treatmen

Quelques études sur l'état et l'évolution de couches minces d'or, en particulier par des mesures de tensions élastiques

A short description is given of investigations on the internal state of gold films, made by means of X-rays and electron microscopie. Presented are elastic strain and stress determinations made by the X-ray line shift method, which gives information about the end of annealing, and by the usual interférence method witch provides a continuous observation of thin films at their early deposition stage.On expose brièvement quelques études menées à l'aide de rayons X, et de la microscopie électronique sur l'état interne de couches minces d'or. On présente ensuite des études de mesure de contraintes et tensions élastiques effectuées par détermination de déplacement de raies X, ce qui donne des renseignements sur la fin du recuit et par interférométrie ordinaire, ce qui permet de suivre l'évolution des couches au début de leur existence

Quelques philosophes emigres ou exiles aux USA devant l'Europe de la deuxieme guerre mondiale L'Ecole de Francfort, Levi-Strauss, Maritain, Rougier, Vignaux, Voegelin

Available at INIST (FR), Document Supply Service, under shelf-number : AR 14415 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc