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 (Figure 1). 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. Consequently, deciphering the mechanisms that underlie RNAPII phosphorylation regulation has become one of the most studied issues in the field of gene expression.
The main goal of our research is to decipher the molecular mechanisms underlying transcription regulation of mRNAs, in general, and RNAPII phosphorylation, in particular. Morevorer, we study some factors involved in transcription termination of snoRNAs and how they interacts with RNAPII machinery.
We are also studying how gene looping is regulated during mRNAs transcription. Gene loops are formed by the interaction of promoters and 3’ end regions in a transcription-dependent manner. This interaction is facilitated by the association of preinitiation factors with termination and 3’ end processing factors (Figure 2, TFIIB, CPF, CFI). Indeed, the formation of gene loops is tightly connected to transcription termination. Moreover, gene loops has an important role in transcription reinitiation, as with these structures RNAPII recruitment is bypassed as the rate-limiting step in the reactivation of transcription. Gene loops are also required for the directionality of transcription and in addition, have been implicated in intron-mediated enhancement of transcription and transcription memory. Finally, we are investigating how RNAPII transcription is coordinated with other nuclear processes, such as the telomere metabolism.
Figure 1. (A) Left: RNAPII structure. Right: Human and S. cerevisiae Rpb1-CTD. (B) Rpb1-CTD phosphorylation profile during the transcription cycle (Calvo and García, 2012. Protein Phosphorylation in Human Health. DOI: 10.5772/48490).
Figure 2. A working model for gene looping: gene loops are formed and maintained at the nuclear pore (NPC) to facilitate the transfer of RNAPII from the terminator to the promoter and promote rapid transcription and therefore export of the messenger to the cytoplasm for translation
Miembros del grupo
|Olga Calvo||Investigador Principal (CSIC)|
|Miguel Carabias||Titulado Superior|
|Noelia González||Titulada Superior|
|Esperanza Miñambres||Estudiante de Máster|
| 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. In press
| 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