tailieunhanh - Báo cáo khoa học: Linking pseudouridine synthases to growth, development and cell competition

Eukaryotic pseudouridine synthases direct RNA pseudouridylation and bind H⁄ACA small nucleolar RNA (snoRNAs), which, in turn, may act as precursors of microRNA-like molecules. In humans, loss of pseudouridine synthase activity causes dyskeratosis congenita (DC), a complex systemic disorder characterized by cancer susceptibility, failures in ribosome biogen-esis and telomere stability, and defects in stem cell formation. | ỊFEBS Journal Linking pseudouridine synthases to growth development and cell competition Giuseppe Tortoriello1 Jose F. de Celis2 and Maria Furia1 1 Dipartimento di Biologia Strutturale e Funzionale University di Napoli Federico II Naples Italy 2 Centro de Biologia Molecular Severo Ochoa Universidad Autonoma de Madrid and Consejo Superior de Investigaciones Cientificas Spain Keywords cell competition dyskeratosis Notch pseudouridine synthase snoRNP Correspondence M. Furia Dipartimento di Biologia Strutturale e Funzionale Universita di Napoli Federico II Complesso Universitario Monte Santangelo via Cinthia 80126 Naples Italy Fax 39 081 679233 Tel 39 081 679072 39 081 679071 39 081 679076 E-mail mfuria@ Present address European Neuroscience Institute at Aberdeen University of Aberdeen Aberdeen UK Received 14 December 2009 revised 24 May 2010 accepted 3 June 2010 doi Eukaryotic pseudouridine synthases direct RNA pseudouridylation and bind H ACA small nucleolar RNA snoRNAs which in turn may act as precursors of microRNA-like molecules. In humans loss of pseudouridine synthase activity causes dyskeratosis congenita DC a complex systemic disorder characterized by cancer susceptibility failures in ribosome biogenesis and telomere stability and defects in stem cell formation. Considering the significant interest in deciphering the various molecular consequences of pseudouridine synthase failure we performed a loss of function analysis of minifly mfl the pseudouridine synthase gene of Drosophila in the wing disc an advantageous model system for studies of cell growth and differentiation. In this organ depletion of the mfl-encoded pseudouridine synthase causes a severe reduction in size by decreasing both the number and the size of wing cells. Reduction of cell number was mainly attributable to cell death rather than reduced proliferation establishing that apoptosis plays a key role in the development of the loss of function mutant .