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Instituto de Parasitología y Biomedicina
"López - Neyra"
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[ Staff | Summary of Research | Funding Agencies | Publications | Doctoral Theses | Patents | Teaching]




mRNA FORMATION AND FUNCTION



Group Leader
    • Carles María Suñé Negre     
        email: csune (@ipb.csic.es)
        Tlf: 958181645



    Staff Research Predoctoral
    • Sofia Boyero Corral     


    Authorized Staff
    • Ana María Cerón Moreno     
    • Younes El Yousfi      
    • Cristina Moreno Castro     
    • Silvia Prieto Sánchez     

     

    SUMMARY OF RESEARCH


     

    Summary

     

    The tightly regulated process of precursor messenger RNA (pre-mRNA) alternative splicing is a key mechanism to increase the number and complexity of proteins encoded by the genome. The results of deep sequencing-based expression analyses suggest that more than 90% of multi-exon human genes undergo alternative splicing. Changes in the cis- or trans- regulation of this process can cause multiple pathologies as a result of general or specific aberrant pre-mRNA processing underscoring the fundamental importance of this regulatory process. Evidence gathered in recent years has established that transcription and splicing are physically and functionally coupled and that this coupling may be an essential aspect of the regulation of splicing and alternative splicing.



    Despite considerable efforts, numerous questions remain regarding the functional significance and global impact of this coupling on cellular and organism homeostasis as well as its underlying molecular mechanisms. In addition to study the molecular events that govern the interactions between the transcription and splicing machineries, we want to go further and provide new insights regarding the molecular mechanisms at work in pathological situations. Our research aims to elucidate the mechanisms of transcription and pre-mRNA processing regulation, which may provide novel and important insights regarding the molecular events that lead to neurological and lymphoproliferative disorders. We also want to identify and characterize the cellular components of these important pathways that should set the groundwork for the understanding of their functions. It is very likely that as this is achieved we will also learn valuable lessons on novel transcriptional/alternative splicing regulatory mechanisms of cellular genes.







     

    1. Transcription/alternative splicing regulation in nervous system

     

    We study the function of WW- and FF-containing proteins in neurogenesis and investigate the molecular mechanism/s by which these factors are affecting the transcription/alternative splicing of endogenous mRNAs that may contribute to the disease phenotype in neurological disorders.









     

    2. Transcription/alternative splicing regulation in cancer

     

    We study the link between the transcription/alternative splicing activity of core spliceosome machinery and the development of haematological malignancies. We are also starting research lines to study the regulation of pre-mRNA splicing in DNA repair, which is essential to maintain genome integrity, to offer new insights into the mechanism of neoplastic transformation.









     

    3. Transcription/alternative splicing regulation in living cells

     

    We investigate the spatial organization and dynamics of transcription and pre-mRNA processing within the highly compartmentalized eukaryotic nucleus, which are fundamental to fully understand how the regulation of gene expression is exerted in the cell.









     


    FUNDING AGENCIES LAST 5 YEARS

    - DEFINIENDO MECANISMOS DE ACOPLAMIENTO ENTRE TRANSCRIPCION Y SPLICING VINCULADOS A ENFERMEDADES DEGENERATIVAS. PROYECTO, PN2017 - PROY I+D+I - PRG. RETOS DE LA SOCIEDAD, Ref: BFU2017-89179-R, (2018 - 2020).

    - Acoplamiento funcional entre la transcripción y el splicing. PROYECTO, PN2014 - PROY I+D+I - PRG. RETOS DE LA SOCIEDAD, Ref: BFU2014-54660-R, (2015 - 2017).

    - Regulación del splicing co-transcripcional en genes de procesos biológicos esenciales. PROYECTO, Proyectos de Excelencia 2012 Junta de Andalucía, Ref: P12-BIO-2515, (2014 - 2018).

    - Papel de TCERG1 de la dendritogénesis de células neuronales. PROYECTO, , Ref: 201320E006, (2013 - 2015).

    - ACOPLAMIENTO DE LA TRANSCRIPCION Y EL SPLICING ALTERNATIVO DE LOS PRE-MRNAS. PROYECTO, PN2011 - I.F.N.O.- BIOLOGÍA FUNDAMENTAL Y DE SISTEMAS, Ref: BFU2011-24577, (2012 - 2014).

    - Acoplamiento bioquímico y funcional entre la transcripción, el procesamiento de los RNAs y la arquitectura nuclear. PROYECTO, PLAN ANDALUZ DE INVESTIGACION, Ref: P09-CVI-4626, (2010 - 2014).

     

     

    PUBLICATIONS LAST 5 YEARS

    -Juan Pablo Muñoz-Cobo; Noemí Sánchez-Hernández; Sara Gutiérrez; Younes El Yousfi; Marta Montes; Carme Gallego; Cristina Hernández-Munain; Carlos Suñé, Transcriptional Elongation Regulator 1 Affects Transcription and Splicing of Genes Associated with Cellular Morphology and Cytoskeleton Dynamics and Is Required for Neurite Outgrowth in Neuroblastoma Cells and Primary Neuronal Cultures, Molecular Neurobiology, 2017, Vol. 54: 7808-7823, ARTICULO, Id:623498

    -Suñé-Pou, M.; Prieto-Sánchez, S.; Boyero-Corral, S.; Moreno-Castro, C.; Yousfi, Y.E.; Suñé-Negre, J.M.; Hernández-Munain, C.; Suñé, C., Targeting splicing in the treatment of human disease, GENES, 2017, Vol. 8: 3-87, ARTICULO DE REVISION, Id:656666

    -Sánchez-Hernández, N.; Prieto-Sánchez, S.; Moreno-Castro, C.; Muñoz-Cobo, J.P.; El Yousfi, Y.; Boyero-Corral, S.; Suñé-Pou, M.; Hernández-Munain, C.; Suñé, C., Targeting proteins to RNA transcription and processing sites within the nucleus, International Journal of Biochemistry and Cell Biology, 2017, Vol. 91: 194-202, ARTICULO DE REVISION, Id:688890

    -Fàbregas, A.; Prieto, S.; Suñé-Pou, M.; Boyero-Corral, S.; Ticó, J.R.; García-Montoya, E.; Pérez-Lozano, P.; Miñarro, M.; Suñé-Negre, J.M.; Hernández-Munain, C.; Suñé, C., Improved formulation of cationic solid lipid nanoparticles displays cellular uptake and biological activity of nucleic acids, International journal of pharmaceutics, 2017, Vol. 516: 39-44, ARTICULO, Id:619452

    -Sánchez-Hernández N; Boireau S; Schmidt U; Muñoz-Cobo JP; Hernández-Munain C; Bertrand E; Suñé C, The in vivo dynamics of TCERG1, a factor that couples transcriptional elongation with splicing, RNA, 2016, Vol. 22: 571-582, ARTICULO, Id:591155

    -Becerra S; Andrés-León E; Prieto-Sánchez S; Hernández-Munain; Suñé C, Prp40 and early events in splice site definition, Wiley Interdisciplinary Reviews - RNA, 2016, Vol. 7: 17-32, ARTICULO DE REVISION, Id:591144

    -Becerra, S.; Montes, M.; Hernández-Munain, C.; Suñe, C., Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and U2AF65and modulates alternative pre-mRNA splicing in vivo, RNA, 2015, Vol. 21: 438-457, ARTICULO, Id:549358

    -Montes, M.; Coiras, M.; Becerra, S.; Moreno-Castro, C.; Mateos, E.; Majuelos, J.; Oliver, F.J.; Hernández-Munain, C.; Alcamí, J.; Suñé, C., Functional consequences for apoptosis by transcription elongation regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing, PLoS ONE, 2015, Vol. 10: 10-e0139812, ARTICULO, Id:607415

    -Fàbregas, A.; Sánchez-Hernández, N.; Ticó, J.R.; García-Montoya, E.; Pérez-Lozano, P.; Suñé-Negre, J.M.; Hernández-Munain, C.; Suñé, C.; Miñarro, M., A new optimized formulation of cationic solid lipid nanoparticles intended for gene delivery: Development, characterization and DNA binding efficiency of TCERG1 expression plasmid, International journal of pharmaceutics, 2014, Vol. 473: 270-279, ARTÍCULO, Id:518470


     

     

    DOCTORAL THESES LAST 5 YEARS

     

    2017

    Juan Pablo Muñoz-Cobo Belart

    Análisis del silenciamiento génico de TCERG1 mediante Exon Arrays

    Instituto de Parasitología y Biomedicina López Neyra CSIC

     

     
    2015

    Soraya Becerra Ortiz

    Caracterización bioquímica y funcional del factor de transcripción y splicing PRPF40B

    IPBLN CSIC

     

     

     

     


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