Biyoinformatik ve Genetik Bölümü Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12469/46

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    Citation - Scopus: 23
    The Drosophila Fragile X Mental Retardation Protein Participates in the Pirna Pathway
    (Company of Biologists Ltd, 2015) Bozzetti, Maria Pia; Specchia, Valeria; Cattenoz, Pierre B.; Laneve, Pietro; Geusa, Annamaria; Şahin, H. Bahar; Di Tommaso, Silvia D.; Friscini, Antonella; Massari, Serafina; Diebold, Celine; Giangrande, Angela
    RNA metabolism controls multiple biological processes and a specific class of small RNAs called piRNAs act as genome guardians by silencing the expression of transposons and repetitive sequences in the gonads. Defects in the piRNA pathway affect genome integrity and fertility. The possible implications in physiopathological mechanisms of human diseases have made the piRNA pathway the object of intense investigation and recent work suggests that there is a role for this pathway in somatic processes including synaptic plasticity. The RNA-binding fragile X mental retardation protein (FMRP also known as FMR1) controls translation and its loss triggers the most frequent syndromic form of mental retardation as well as gonadal defects in humans. Here we demonstrate for the first time that germline as well as somatic expression of Drosophila Fmr1 (denoted dFmr1) the Drosophila ortholog of FMRP are necessary in a pathway mediated by piRNAs. Moreover dFmr1 interacts genetically and biochemically with Aubergine an Argonaute protein and a key player in this pathway. Our data provide novel perspectives for understanding the phenotypes observed in Fragile X patients and support the view that piRNAs might be at work in the nervous system. © 2015.
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    Article
    Citation - WoS: 47
    Citation - Scopus: 49
    New Insights Into the Regulatory Function of Cyfip1 in the Context of Wave- and Fmrp-Containing Complexes
    (Company of Biologists Ltd, 2017) Abekhoukh, Sabiha; Şahin, H. Bahar; Grossi, Mauro; Zongaro, Samantha; Maurin, Thomas; Madrigal, Irene; Kazue-Sugioka, Daniele; Raas-Rothschild, Annick; Doulazmi, Mohamed; Carrera, Pilar; Stachon, Andrea; Scherer, Steven; Do Nascimento, Maria Rita Drula; Trembleau, Alain; Arroyo, Ignacio; Szatmari, Peter; Smith, Isabel M.; Mila, Montserrat; Smith, Adam C.; Giangrande, Angela; Caille, Isabelle; Bardoni, Barbara
    Cytoplasmic FMRP interacting protein 1 (CYFIP1) is a candidate gene for intellectual disability (ID) autism schizophrenia and epilepsy. It is a member of a family of proteins that is highly conserved during evolution sharing high homology with its Drosophila homolog dCYFIP. CYFIP1 interacts with the Fragile X mental retardation protein (FMRP encoded by the FMR1 gene) whose absence causes Fragile X syndrome and with the translation initiation factor eIF4E. It is a member of theWAVE regulatory complex (WRC) thus representing a link between translational regulation and the actin cytoskeleton. Here we present data showing a correlation between mRNA levels of CYFIP1 and other members of the WRC. This suggests a tight regulation of the levels of the WRC members not only by post-translational mechanisms as previously hypothesized. Moreover we studied the impact of loss of function of both CYFIP1 and FMRP on neuronal growth and differentiation in two animal models -fly and mouse. We show that these two proteins antagonize each other's function not only during neuromuscular junction growth in the fly but also during new neuronal differentiation in the olfactory bulb of adult mice. Mechanistically FMRP and CYFIP1 modulate mTor signaling in an antagonistic manner likely via independent pathways supporting the results obtained in mouse as well as in fly at the morphological level. Collectively our results illustrate a new model to explain the cellular roles of FMRP and CYFIP1 and the molecular significance of their interaction.