Gene Expression and RNA Metabolism
My laboratory is interested in understanding the functional crosstalk of distinct steps of the gene expression pathway. Gene expression is the most crucial cellular process as it is the fundamental mechanism for translating the static DNA information into life. It is a coordinated multistep process in which distinct protein complexes exert pivotal functions at different levels.
Among them we are investigating the role of of the transcriptional co-activator SAGA complex and the nuclear pore associated machinery TREX-2. SAGA participates in the regulation of stress-induced genes of distinct types of signaling pathways and TREX-2 is involved in mRNA metabolism, export and genome stability.
Most of our efforts are directed to understand the role of Sus1, the shared factor between SAGA and TREX-2. Sus1 is a conserved factor through the eukaryotic kingdom. The research done to address the role of Sus1/ENY2 has provided in deep description of different mechanisms influencing gene expression. Although the role of Sus1 in human cells is largely unknown, preliminary results suggest interesting links to pathological states that range from cancer, rare diseases and diabetes. Since SAGA and TREX-2 have key roles in fundamental physiological processes, it is unsurprising that they are involved in the etiology of human diseases. Our work will help us to understand how they impact/affect human health.
A novel role for Sem1 and TREX-2 in transcription involves their impact on recruitment and H2B deubiquitylation activity of SAGA.
García-Oliver E, Pascual-García P, García-Molinero V, Lenstra TL, Holstege FC, Rodríguez-Navarro S
Nucleic acids research , 2013 Jun, vol. 41, pag. 5655-68
SUS1 introns are required for efficient mRNA nuclear export in yeast.
Cuenca-Bono B, García-Molinero V, Pascual-García P, Dopazo H, Llopis A, Vilardell J, Rodríguez-Navarro S
Nucleic acids research , 2011 Oct, vol. 39, pag. 8599-611, Impact Factor: 8.026
Sus1 is recruited to coding regions and functions during transcription elongation in association with SAGA and TREX2.
Pascual-García P, Govind CK, Queralt E, Cuenca-Bono B, Llopis A, Chavez S, Hinnebusch AG, Rodríguez-Navarro S
Genes & development , 2008 Oct 15, vol. 22, pag. 2811-22
The mRNA export factor Sus1 is involved in Spt/Ada/Gcn5 acetyltransferase-mediated H2B deubiquitinylation through its interaction with Ubp8 and Sgf11.
Köhler A, Pascual-García P, Llopis A, Zapater M, Posas F, Hurt E, Rodríguez-Navarro S
Molecular biology of the cell , 2006 Oct, vol. 17, pag. 4228-36
Sus1, a functional component of the SAGA histone acetylase complex and the nuclear pore-associated mRNA export machinery.
Rodríguez-Navarro S, Fischer T, Luo MJ, Antúnez O, Brettschneider S, Lechner J, Pérez-Ortín JE, Reed R, Hurt E
Cell , 2004 Jan 9, vol. 116, pag. 75-86