Regulation of gene expression is the result of the combined control of transcription and RNA processing in the nucleus, as well as translation and mRNA decay in the cytoplasm. One of these processes, transcription of protein-encoding genes by RNA polymerase II (RNAPII), plays a central role in gene expression in all living organisms. RNAPII transcription is highly regulated at many steps, including initiation, elongation and termination, and tightly coordinated and linked to many other nuclear functions in a complex web of connections. The central coordinator that directs this regulatory network is the RNAPII itself, being the carboxy-terminal domain (CTD) of its largest subunit, Rpb1, of remarkable importance. Thus, RNAPII-CTD phosphorylation regulates and coordinates the entire transcription cycle with pre-mRNA processing and mRNA transport, and with chromatin remodeling and histone modifications. Therefore, RNAPII phosphorylation is one of the key processes in the regulation of gene expression in general. Whether other RNAPII subunits are subjected to phosphorylation and its relevance in gene transcription is unknown. In the case of RNAPI and RNAPIII, which not contain a CTD domain, little is known about their regulation by phosphorylation, and whether this is a mechanism that could be used to connect and coordinate RNAPs activity. Consequently, deciphering the mechanisms underlying RNAPs phosphorylation regulation is key to understand gene expression regulation.
In our group, we study:
1.-The molecular mechanisms underlying transcription regulation of mRNAs, such as RNAPII phosphorylation and gene loops formation.
2.-The connection of RNAPII transcription in the nucleus to translation and mRNA decay in the cytoplasm through the stalk domain, consisting of Rpb4 and Rpb7.
3.-New factors shared by the three eukaryotic RNAPs.
Figure 1. (A) RNAPII structure. Ribbon representation of two views of Saccharomyces cerevisiae RNAPII (PDB: 1y1w), displaying phospho-sites identified in proteomic studies, with unknown function. They are labelled in different colors according to the 12 subunits diagram. RNAPII mobile modules are indicated with white open circles (González-Jiménez, 2021). (B) Processes regulated by the Rpb4/7 heterodimer (Calvo, 2020). (C) RNAPI structure displaying phospho-sites (PDB: 4c3h), represented as in A (González-Jiménez et al. 2021). (D) RNAPIII structure showing phospho-sites (PDB: 5fj9) represented as in A (González-Jiménez et al. 2021).
|Olga Calvo||Principal Investigator (CSIC)|
|Mª del Carmen González||Postdoctoral|
|Araceli González||PhD Student|
|Manuel Jesús Alfonso||Laboratory Technician|
| González-Jiménez, A, Campos A, Navarro F, Clemente-Blanco A and Calvo O. (2021).
Regulation of eukaryotic RNAPs activities by phosphorylation. The Lesser Known World of RNA Polymerases.
Frontiers in Molecular Biosciences.
| Calvo O. (2020).
RNA polymerase II phosphorylation and gene looping: new roles for the Rpb4/7 heterodimer in regulating gene expression.
Current Genetics. 66: 927-937
| Allepuz-Fuster P, O'Brien M, González-Polo N, Pereira B,Dhoondia Z; Ansari A, Calvo O. (2019).
RNA polymerase II plays an active role in the formation of gene loops through the Rpb4 subunit.
Nucleic Acids Research. 47: 8975–8987
| Calvo O*, Grandin N, Jordan-Pla A, Minambres E, Gonzalez-Polo N, Pérez-Ortín JE, Charbonneau M*. (2019).
The telomeric Cdc13-Stn1-Ten1 complex regulates RNA polymerase II transcription
Nucleic Acids Research. 47(12):6250-6268
| Sanz-Murillo M, Xu J, Belogurov GA, Calvo O, Gil-Carton D, Moreno-Morcillo M, Wang D, Fernández-Tornero C. (2018).
Structural basis of RNA polymerase I stalling at UV light-induced DNA damage.
Proc Natl Acad Sci U S A. 115(36):8972-8977.
| O. Calvo (2018).
Sub1 and RNAPII, until termination does them part.
Transcription. 9: 52-60.
| Torreira E, Louro JL, Pazos I, González-Polo N, Gil-Carton D, Garcia-Duran A, Tosi S, Gallego O*, Calvo O*, Fernández-Tornero, C*. (2017).
The dynamic assembly of distinct RNAP I complexes modulates rDNA transcription.
| Garavís M, González-Polo N, Allepuz-Fuster P, Louro JA, Fernández-Tornero C, Calvo O. (2017).
Sub1 contacts the RNA polymerase II stalk to modulate mRNA synthesis
Nucleic Acids Research. 45: 2458-71.
| M. Garavís and Calvo O. (2017).
Sub1/PC4, a multifaceted factor:from transcription to genome stability.
Current Genetics. 63:1023-1035.
| Franco-Echevarría E, González-Polo N, Zorrilla S, Martínez-Lumbreras S, Clara M Santiveri CM, Campos-Olivas R, Sánchez M, Calvo O, González B, Pérez-Cañadillas JM. (2017).
The structure of transcription termination factor Nrd1 reveals an original mode for GUAA recognition.
Nucleic Acids Research. 45:10293-10305.
| Allepuz-Fuster P, Martínez-Fernández, V, Garrido-Godino AI, Alonso-Aguado S, Hanes SD, Navarro F and Calvo O. (2014).
Rpb4/7 facilitates RNA polymerase II CTD dephosphorylation.
Nucleic Acids Research. 42: 13674-13688.
Proyectos de investigación
|I-LINK 2018||I-LINK 1213|