Gene expression and RNA metabolism
Susana Rodríguez Navarro. My research is focussed on studying the mechanisms that control gene expression. My Ph.D. (1996-2000) investigated the function of unknown genes in S. cerevisiae. Some of my results motivated me to study deeper mRNA processing. Therefore, I pursued with my postdoctoral formation supervised by Ed Hurt, working on mRNA processing in Germany.
I studied mRNA export and the possible connection with early events during gene expression. I participated in a total of 8 publications. Our findings were outstanding allowing their publication in top impact factor journals as Cell, Nature, NCB and EMBO J. Then, I initiated an independent research group: Gene expression and RNA metabolism in 2005 at CIPF.
Very recently I moved to the Instituto de Biomedicina de Valencia (IBV-CSIC) where the group continue with its scientific aims in new environment oriented to understanding the molecular bases of human diseases and to improve the fundamental knowledge in the topic of gene expression and RNA metabolism.
For 13 years, my lab has researched in the mechanisms of mRNA transport and epigenetic control in the model system S. cerevisiae. In 2017-18 my lab consists of 1 postdoc, 5 PhD students, 1 master student and 2 undergraduate students, along with the collaborations with several national & international laboratories. I have a successful career in the gene expression and mRNA biogenesis field. My major achievements are the discoveries related to the characterization of Sus1 and the processes in which it is involved. My works with this protein and others complexes as SAGA and TREX2 have unveiled chromatin remodeling and post-transcriptional mechanisms necessary for mRNA genesis and nuclear export. I published a total of 38 articles with more than 2200 cites. During the last 7 years, I published 16 articles in journals as EMBO Reports, Nucleic Acid Research, Epigenetics & Chromatin, Genome Research, PloS Genetics, RNA, BBA-GRM and Molecular and Cellular Biology. In 10/1616 publications I am senior author. I have). As team leader, I raised grants up to 1.4 m€ from public and private institutions. I imparted invited oral presentations in international conferences, research institutions and scientific meetings. I have also been invited to contribute with Revision papers and acted as Guest editor of BBA-GRM.
I received the IZASA-WERFEN award from the Spanish Society of Biochemistry and Molecular Biology as an outstanding Spanish biochemist for my discoveries as an independent group.
In the last years, my work has been awarded with different grants including a network of excellence in which I act as PI aiming to create synergies with other researchers and groups within Spain. I have a large training & teaching experience. I supervised 6 PhDs (3 more ongoing), 5 postdoc, 7 TFM and 3 TFGs. I have participated as a full member in the supervising committee of two PhD programs one at the University of Valencia and Polytechnic University of Valencia. I have participated in different committees to evaluate National and International grants, IP positions and fellowships (EC, Spain, France, UK and Holland.) In addition, I become scientific co-director of the CIPF and director of the Department of “Molecular bases of disease.
I am also committed to science dissemination to general audience and to motivate young females to pursue a scientific career. Therefore, I participate actively in many actions including talks, writing and radio programs.
- Manuel Martín Expósito
- Carme Nuño Cabanes
- Joan Serrano Quilez
- Ileana Serra
- Lucía Casares
Complex programs of gene expression delineate cellular identity, growth and response to stimuli. These programs are the result of interconnected steps that are regulated by the action of a myriad of factors and activities. Over the past twenty years, studies in many laboratories have discovered some of them. However, many molecular and functional aspects of the process remain unknown.
Eukaryotic gene expression is a complex process regulated at multiple levels, including nuclear and cytoplasmic events. These levels comprise different linked steps such as chromatin modifications, transcription, RNA processing, export to the cytoplasm, translation and degradation of mRNAs. A precise regulation of gene expression is vital to establishing the metabolic activities in every living cell in all organisms. Therefore, discovering the elements (factors and mechanisms) dictating these expression patterns is fundamental to understand how most cellular processes are accomplished. Our work has contributed to discover some of these elements. We were interested in understanding to which extent S.cerevisiae Sus1, a functional component of the SAGA/SLIK histone acetylase complex that participates in epigenetic regulation and the nuclear pore-associated mRNA export machinery TREX-2, contributes to gene expression. The study of these two complexes permitted the identification of new elements. However, we still do not have a complete picture of how epigenetic regulation is crucial to determine mRNA fate. Studies linking the different levels of gene expression have been the focus of intense research. Notably, an increasing number of studies revealed that dynamics of chromatin structure influences mRNP formation and fate. This role is beyond the well-known participation of chromatin in all DNA related processes like for instance replication, repair or transcription. Chromatin is formed by DNA and histone proteins whose tails are extensively “marked” by post-translational modifications (PTMs). These marks are dynamically incorporated and removed by a group of “writers” and “erasers” which determine the epigenetic code. Most of the studies have shown how nucleosome organization and the combination of histone marks strongly affect mRNP processing. Therefore, specific expression patterns can be achieved by the cell through controlling chromatin modifications linked to mRNP processing. In this sense, it might be very important for cell adaptation to stress or differentiation. Among the connections between chromatin and mRNA processing events, our lab has been mostly interested in the chromatin modifications achieved by the SAGA coactivator and mRNA export by studying TREX-2. We aspire to answer some of the open questions bringing further our knowledge of how SAGA/SLIK/TREX-2 and new factors discovered in our previous work participate in coordinating gene expression steps. Interestingly, the dysfunction of these machineries leads to several pathological states. Actually, mutations in these factors contribute to human diseases that range from Spinocerebellar ataxia type 7 Brugada syndrome and cancer, to diabetes. Our work has relevance to both the understanding of important biological processes as well as their possible future implications in human pathologies. Altogether, this will result in a significant advance in the state of the art of the gene expression regulation