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Mechanisms of Disease

Translational Control of Cell Cycle and Differentiation

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Group Leader
Telephone:
+34 93 40 31900

ICREA Research Professor

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ICREA

Research information

Background

Recent years have seen a paradigm shift in our understanding of gene activity and regulation. It is now clear that processing of primary transcripts as well as translational control open a myriad of opportunities for gene regulation, which are extensively used in virtually every human gene. However, how these events are regulated and how alterations of these finely tuned processes contribute to physio/pathological processes is not yet well understood.

The primary interest of our group has been to understand the molecular mechanisms that dictate alternative 3’ UTR formation and the temporal and spatial translational control of specific mRNAs during cell cycle progression and chromosome segregation, senescence and related pathologies. Cell cycle progression is programmed, at least in part, by stored silent mRNAs. These mRNAs are not translated en masse at any one time, or even at any one place; rather, their translation is specifically regulated by sequences located at their 3´-untranslated regions (3´-UTRs) and their binding proteins.

Research lines

Our work focuses on four main lines of research:

First, to elucidate the mechanisms underlying the translational control by cytoplasmic polyadenylation cis-acting elements and trans-acting factors:
1) Genome-wide identification of the mRNAs that are regulated by nuclear and cytoplasmic changes in their poly(A) tail length;
2) Determination of the configuration of cis-acting elements that define the temporal and spatial translational regulation;
3) Functional and structural characterization of the ribonucleoprotein (RNPs) complexes that mediate this translational regulation.

Second, to obtain insights in how this translational control circuit regulates cell cycle progression by establishing a molecular circuit, stabilized by positive and negative feed-back loops to generate an irreversible self sustain hysteric system with molecular memory and switch-like phase transitions.

Third, to explore the role of these mRNA processing and translation mechanisms in the reprogramming of gene expression in tumoral events and angiogenesis and the development of tools with prognostic and therapeutic value.

Forth, to study the symmetric distribution of cellular components (research directed by Oriol Gallego, see www.gallegolab.org)
1)A comparative analysis of Multisubunit Tethering Complexes
2)Characterize the interplay between the transport of vesicles and mRNA localization

Selected publications

Duran-Arqué, Berta; Cañete, Manuel; Castellazzi, Chiara Lara; Bartomeu, Anna; Ferrer-Caelles, Anna; Reina, Oscar; Caballé, Adrià; Gay, Marina; Arauz-Garofalo, Gianluca; Belloc, Eulalia; Mendez, Raúl
Genome Biology
23
(1 )
192 -
(2022)
Suñer, Clara; Sibilio, Annarita; Martín, Judit; Castellazzi, Chiara Lara; Reina, Oscar; Dotu, Ivan; Caballé, Adrià; Rivas, Elisa; Calderone, Vittorio; Díez, Juana; Nebreda, Angel R; Méndez, Raúl
Elife
11
(2022)
Pascual, Rosa; Martin, Judit; Salvador, Fernando; Reina, Oscar; Chanes, Veronica; Millanes-Romero, Alba; Suner, Clara; Fernandez-Miranda, Gonzalo; Bartomeu, Anna; Huang, Yi-Shuian; Gomis, Roger R; Mendez, Raul
Science Advances
6
(20 )
eaax3868 -
(2020)
Parras A, Anta H, Santos-Galindo M, Swarup V, Elorza A, Nieto-González JL, Picó S Hernández IH, Díaz-Hernández JI, Belloc E, Rodolosse A, Parikshak NN, Peñagarikano O, Fernández-Chacón R, Irimia M, Navarro P, Geschwind DH, Méndez R*, Lucas JJ*. (* co-corresponding authors).
Nature
560
(7719 )
441 -
+
(2018)
Weill L; Belloc E; Castellazzi CL; Méndez R
Nature Structural & Molecular Biology
24
(8 )
672 -
+
(2017)
Maillo, Carlos; Martin, Judit; Sebastian, David; Hernandez-Alvarez, Maribel; Garcia-Rocha, Mar; Reina, Oscar; Zorzano, Antonio; Fernandez, Mercedes; Mendez, Raul
Nature Cell Biology
19
(2 )
94 -
105
(2017)
Guillén-Boixet J; Buzon V; Salvatella X; Méndez R
Elife
5
(e19298 )
e19298 -
(2016)
Calderone V, Gallego J, Fernandez-Miranda G, Garcia-Pras E, Maillo C, Berzigotti A, Mejias M, Bava FA, Angulo-Urarte A, Graupera M, Navarro P, Bosch J, Fernandez M, Mendez R
Gastroenterology
150
(4 )
982 -
+
(2016)
Afroz T; Skrisovska L; Belloc E; Guillén-Boixet J; Méndez R; Allain F
Genes & Development
28
(13 )
1498 -
1514
(2014)
Bava, Felice-Alessio; Eliscovich, Carolina; Ferreira, Pedro G; Minana, Belen; Ben-Dov, Claudia; Guigo, Roderic; Valcarcel, Juan; Mendez, Raul
Nature
495
(7439 )
121 -
125
(2013)
Ortiz-Zapater, Elena; Pineda, David; Martinez-Bosch, Neus; Fernandez-Miranda, Gonzalo; Iglesias, Mar; Alameda, Francesc; Moreno, Mireia; Eliscovich, Carolina; Eyras, Eduardo; Real, Francisco X; Mendez, Raul; Navarro, Pilar
Nature Medicine
18
(1 )
83 -
90
(2012)
Novoa I; Gallego J; Ferreira P; Mendez R
Nature Cell Biology
12
(5 )
447 -
U82
(2010)
Eliscovich C; Peset I; Vernos I; Méndez R
Nature Cell Biology
10
(7 )
858 -
865
(2008)
Piqué M; López J; Foissac S; Guigó R; Méndez R
Cell
132
(3 )
434 -
448
(2008)

Projects

Grup de Recerca consolidat Translational Control of Cell Cycle and Differentiation funded by the Agencia de Gestió d'Ajuts Universitaris i de Recrerca (AGAUR) 2014 SGR 0127

Generalitat de Catalunya

 

 

 


"Estudio combinatorial de los circuitos de expresión génica establecidos por la familia CPEB de proteinas de unión a RNA: mecanismos deacción y nuevas funciones celulares" funded by Ministerio de Economia y Competitividad and Fondo Europeo de Desarrollo Regional (FEDER) de la Unión Europea. BFU2014-54122-P

Ministerio de Economio y Competitividad

 

 

 


"Molecular regulation of the progression from hepatic steatosis to cirrhosis and hepatocellular carcinoma: Role and therapeutic potential of CPEB proteins" funded by Fundación Científica Asociación Española contra el Cancer (AECC) GCB15152955MÉND

AECC

 

 

 


"Role and therapeutic potential of CPEB proteins in the transition from cirrhosis to hepatocellular carcinoma" funded by Worldwide Cancer Research  (WCR) 16-0026

Worldwide Cabcer Research

 

 

 


Grup de Recerca consolidat (SGR 2017-2019) Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement de la Generalitat de Catalunya. Agencia de Gestió d'Ajuts Universitaris i de Recerca (AGAUR). Reference: 2017 SGR 1451

Generalitat de Catalunya

 

 

 


"Regulación traduccional de la división celular, la diferenciación y el cancer: análisis in vivo de las funciones y mecanismos de acción de las CPEBS" funded by Ministerio de Ciencia e Innovación - Agencia Estatal de Investigación and Fondo Europeo de Desarrollo Regional (FEDER) de la Unión Europea. BFU2017-83561-P

Ministerio de ciencia e innovación, Unión Europea, Agencia estatal de investigación

 

 

 


"Metabolic reprogramming in obesity-drven liver cancer, mechanisms, functions and therapeutic potential" AYUDAS FUNDACIÓN BBVA A EQUIPOS DE INVESTIGACIÓN CIENTÍFICA 2018

Fundaciçon BBVA

 

 

 


 "Normalization of tumor vasculature through pharmacological inhibition of p38a: Effect on chemotherapeutic drug delivery" funded by Fundació Bancaria Caixa d'Estalvis i Pensions (La Caixa) LCF/PR/HR19/52160020

Fundación la Caixa

 

 

 


"Reprogramació metabòlica del càncer de fetge basat en l'obesitat: mecanismes, funcions i oportunitats terapèutiques" funded by Fundació La Marató TV3. 201926-30

 

 

 


 "Targeting CPEB-mediated translational balance in Hepatocellular Carcinoma" funded by Worldwide Cancer Research  (WCR) 20-0284

Worldwide Cabcer Research

 

 

 


"Control traduccional mediado por CPEBs en la interacción tumor-nicho: Una perspectiva mecanística"  funded by Ministerio de Ciencia e Innovación - Agencia Estatal de Investigación PID2020-119533GB-I00

 

 

 


"Desarrollo de inhibidores de CPEB con propiedades antitumorales" funded by the project PDC2021-121716-I00, funded by MCIN/AEI/10.13039/501100011033 and by the European Union “NextGenerationEU”/PRTR”

Ministerio de ciencia e innovación, Unión Europea, Agencia estatal de investigación

Group members

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