Centro Andaluz de Biología Molecular y Medicina Regenerativa

Transcription and mRNA processing

During transcription elongation, the RNA polymerase II (RNAPII) has to overcome obstacles such as the presence of nucleosomes or the topological stress produced by the movement of the transcription complex. My work has been focused on how RNAPII coordinates transcription with the removal of those obstacles. I am particularly interested in studying whether the pauses that are associated to nucleosome remodeling or supercoiling removal could serve as a mechanism for the coupling of transcription elongation with pre-mRNA processing.

We have discovered that positioning of the first (+1) nucleosome in a gene participates in the regulation of promoter-proximal pausing, a highly-regulated pause that takes place in early elongation. Interestingly, in the absence of such nucleosome pre-mRNA capping is affected (Jimeno-González, 2015#1). Furthermore, disrupting chromatin structure globally by histone depletion accelerates transcription rate and, as a consequence, splicing defects are observed (Jimeno-González et al, 2015#2). From a different point of view, I have been focused on how changing DNA supercoiling levels by topoisomerase II inhibition alters transcription regulation obtaining results that point to a deep relevance of DNA topology in the control of different transcriptional steps.

Previous positions:

  • Postdoctoral researcher with Felipe Cortés-Ledesma, CABIMER (2015-2016)
  • “Juan de la Cierva” researcher with Dr. José Carlos Reyes, CABIMER (2011-2014)
  • Postdoctoral researcher with Prof. Torben Heick Jensen, Aarhus University (2007-2011)
  • PhD student with Prof. Sebastián Chávez, Universidad de Sevilla (2001-2007)

 

ORCID: 0000-0002-6223-9573
Researcher ID: C-2207-2017
Scopus: 15132366300

  • Álvarez-Quilón A, Terrón-Bautista J, Delgado-Sainz I, Serrano-Benítez A, Romero-Granados R, Martínez-García P, Jimeno-González S, Bernal-Lozano C, Quintero C, García-Quintanilla L and Cortés-Ledesma F. Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency. Nature Communications. 2020. In press.
  • Feng W, Kawauchi D, Körkel-Qu H, Deng H, Serger E, Sieber L, Harim Y, Lieberman JA, Jimeno-González S, Lambo S, Hanna B, Jansen M, Neuerburg A, Friesen O, Zuckermann M, Rajendran V, Gronych J, Ayrault O, Korshunov A, Jones DTW, Kool M, Northcott PA, Lichter P, Cortés-Ledesma F, Pfister SM, Liu HK. The chromatin remodeler Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation program. Nature Communications. 2017. Mar 20;8:14758
  • Prado F, Jimeno-González S, Reyes JC. Histone availability as a strategy to control gene expression. RNA Biology. 2016 May 21:1-6.
  • Jimeno-González S*, Reyes JC*. Chromatin structure and pre-mRNA processing work together. Transcription. 2016 May 26;7(3):63-8.
    *Corresponding authors
  • Jimeno-González S*, Payán-Bravo L, Muñoz-Cabello AM, Guijo M, Gutierrez G, Prado F, Reyes JC*. Defective histone supply causes changes in RNA polymerase II elongation rate and cotranscriptional pre-mRNA splicing. Proc Natl Acad Sci U S A. 2015 Dec 1;112(48):14840-5.
    *Corresponding authors
  • Jimeno-González S*, Ceballos-Chávez M, Reyes JC*. A positioned +1 nucleosome enhances promoter-proximal pausing. Nucleic Acids Res. 2015 Mar 31;43(6):3068-78.
    *Corresponding authors
  • Jimeno-González S, Schmid M, Malagón F, Haaning LL and Jensen TH. Rat1p maintains RNA polymerase II CTD phosphorylation balance. RNA. 2014 Apr;20(4):551-8.
  • Jimeno-González S, Haaning LL, Malagón F and Jensen TH. The yeast 5’-3’ exonuclease Rat1p functions during transcription elongation by RNA Polymerase II. Mol Cell. 2010 Feb 26;37(4):580-7.
  • Pelechano V, Jimeno-González S, Rodríguez-Gil A, García-Martínez J, Pérez-Ortín JE and Chávez S. Regulon-specific control of transcription elongation across the yeast genome. PLoS Genet. 2009 Aug;5(8):e1000614.
  • Mas G, de Nadal E, Dechant R, de la Concepción ML, Logie C, Jimeno-González S, Chávez S, Ammerer G and Posas F. Recruitment of a chromatin remodelling complex by the Hog1 MAP kinase to stress genes. EMBO J. 2009 Feb 18;28(4):326-36.
  • Vanti M, Gallastegui E, Respaldiza I, Rodríguez-Gil A, Gómez-Herreros F, Jimeno-González S, Jordan A and Chávez S. Yeast genetic analysis reveals the involvement of chromatin reassembly factors in repressing HIV-1 basal transcription. PLoS Genet. 2009 Jan;5(1):e1000339.
  • Jimeno-González S, Gómez-Herreros F, Alepuz PM and Chávez S. A gene-specific requirement for FACT during transcription is related to the chromatin organization of the transcribed region. Mol Cell Biol. 2006 Dec;26(23):8710-21.

Group leader:
Postdoctorals:
  • Dr. Sabrina Rivero Canalejo
PhD students:
  • Alberto León Halcón
  • Clara Megías Fernández
Technicians:
  • Irene Delgado Sainz