nuclear mrna degradation pathway(s) are implicated in xist regulation and x chromosome inactivation核信使rna降解途径(s)是涉及xist监管和x染色体失活.pdfVIP

Nuclear mRNA Degradation Pathway(s) Are Implicated in Xist Regulation and X Chromosome Inactivation 1 ` 1 2 3 1 1* Constance Ciaudo , Agnes Bourdet , Michel Cohen-Tannoudji , Harry C. Dietz , Claire Rougeulle , Philip Avner ´ ´ ´ ´ ´ ´ 1 Unite de Genetique Moleculaire Murine, Institut Pasteur, Paris, France, 2 Unite de Biologie du Developpement, Institut Pasteur, Paris, France, 3 Institute of Genetic Medicine and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America A critical step in X-chromosome inactivation (XCI), which results in the dosage compensation of X-linked gene expression in mammals, is the coating of the presumptive inactive X chromosome by the large noncoding Xist RNA, which then leads to the recruitment of other factors essential for the heterochromatinisation of the inactive X and its transcriptional silencing. In an approach aimed at identifying genes implicated in the X-inactivation process by comparative transcriptional profiling of female and male mouse gastrula, we identified the Eif1 gene involved in translation initiation and RNA degradation. We show here that female embryonic stem cell lines, silenced by RNA interference for the Eif1 gene, are unable to form Xist RNA domains upon differentiation and fail to undergo X- inactivation. To probe further an effect involving RNA degradation pathways, the inhibition by RNA interference of Rent1, a factor essential for nonsense-mediated decay and Exosc10, a specific nuclear component of the exosome, was analysed and shown to similarly impair Xist upregulat