S.Millevoi

  RNA-binding proteins and post-transcriptional regulation in cancer

 

 

 

 

 

 

 

Our research project at a glance

Post-transcriptional gene expression is deregulated in cancer resulting in altered programs of protein biosynthesis that can drive tumor progression and resistance to therapy. Our research program brings together clinicians, biologists and experts in biostatistics to unveil how molecular mechanisms of translational regulation by RNA-binding proteins are orchestrated in cancer cells and are linked to patient outcome.

Objectives

 

Alteration of post-transcriptional gene expression regulation is a hallmark of cancer. RNA-binding proteins (RBPs) are master regulators required for all post-transcriptional processes, including transcript maturation, mRNA stability and translation. These factors allow dynamic regulation in normal and various stress conditions, and contribute to deregulations in the RNA metabolism of cancer cells. They can also directly impact genome instability by establishing a direct link between DNA- and RNA-mediated processes. RBPs recognize specific elements of diverse sequences and structures. Among these, RNA G-quadruplex structures have been shown to affect the expression of cancer relevant genes by modulating post-transcriptional steps.

Our research focuses on understanding the role of RBPs in post-transcriptional gene expression reprogramming in response to stress and to the deregulation associated to cancer pathobiology.

Our objectives are:

  • to provide a mechanistic and functional understanding into how RBPs impact on cancer development, progression and treatment,
  • to improve our understanding of RNA G-quadruplexes regulation and targeting in cancer cells,
  • to investigate the emerging concept that DNA-damage proteins, beside effects on DNA and signaling, target mRNAs to regulate post-transcriptional gene expression.

 

Key words

 

  • Post-transcriptional gene expression
  • mRNA
  • RNA-binding proteins
  • mRNA translation
  • DNA damage response
  • RNA G-quadruplex structure

 

Selected publications


2017

Cammas, A; Millevoi, S

RNA G-quadruplexes: emerging mechanisms in disease Journal Article

Nucleic Acids Res, 45 (4), pp. 1584-1595, 2017, ISSN: 1362-4962 (Electronic) 0305-1048 (Linking).

Links | BibTeX

2016

Cammas, A; Lacroix-Triki, M; Pierredon, S; Le Bras, M; Iacovoni, J S; Teulade-Fichou, M P; Favre, G; Roche, H; Filleron, T; Millevoi, S; Vagner, S

hnRNP A1-mediated translational regulation of the G quadruplex-containing RON receptor tyrosine kinase mRNA linked to tumor progression Journal Article

Oncotarget, 7 (13), pp. 16793-805, 2016, ISSN: 1949-2553 (Electronic) 1949-2553 (Linking).

Links | BibTeX

Chu, J; Cargnello, M; Topisirovic, I; Pelletier, J

Translation Initiation Factors: Reprogramming Protein Synthesis in Cancer Journal Article

Trends Cell Biol, 26 (12), pp. 918-933, 2016, ISSN: 1879-3088 (Electronic) 0962-8924 (Linking).

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Gandin, V; Masvidal, L; Cargnello, M; Gyenis, L; McLaughlan, S; Cai, Y; Tenkerian, C; Morita, M; Balanathan, P; Jean-Jean, O; Stambolic, V; Trost, M; Furic, L; Larose, L; Koromilas, A E; Asano, K; Litchfield, D; Larsson, O; Topisirovic, I

mTORC1 and CK2 coordinate ternary and eIF4F complex assembly Journal Article

Nat Commun, 7 , pp. 11127, 2016, ISSN: 2041-1723 (Electronic) 2041-1723 (Linking).

Links | BibTeX

Lamaa, A; Le Bras, M; Skuli, N; Britton, S; Frit, P; Calsou, P; Prats, H; Cammas, A; Millevoi, S

A novel cytoprotective function for the DNA repair protein Ku in regulating p53 mRNA translation and function Journal Article

EMBO Rep, 17 (4), pp. 508-18, 2016, ISSN: 1469-3178 (Electronic) 1469-221X (Linking).

Links | BibTeX

2014

Cammas, A; Sanchez, B J; Lian, X J; Dormoy-Raclet, V; van der Giessen, K; Lopez de Silanes, I; Ma, J; Wilusz, C; Richardson, J; Gorospe, M; Millevoi, S; Giovarelli, M; Gherzi, R; Di Marco, S; Gallouzi, I E

Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation Journal Article

Nat Commun, 5 , pp. 4190, 2014, ISSN: 2041-1723 (Electronic) 2041-1723 (Linking).

Links | BibTeX

Sesen, J; Cammas, A; Scotland, S J; Elefterion, B; Lemarie, A; Millevoi, S; Mathew, L K; Seva, C; Toulas, C; Moyal, E C; Skuli, N

Int6/eIF3e is essential for proliferation and survival of human glioblastoma cells Journal Article

Int J Mol Sci, 15 (2), pp. 2172-90, 2014, ISSN: 1422-0067 (Electronic) 1422-0067 (Linking).

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Tcherkezian, J; Cargnello, M; Romeo, Y; Huttlin, E L; Lavoie, G; Gygi, S P; Roux, P P

Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5'TOP mRNA translation Journal Article

Genes Dev, 28 (4), pp. 357-71, 2014, ISSN: 1549-5477 (Electronic) 0890-9369 (Linking).

Links | BibTeX

2011

Decorsiere, A; Cayrel, A; Vagner, S; Millevoi, S

Essential role for the interaction between hnRNP H/F and a G quadruplex in maintaining p53 pre-mRNA 3'-end processing and function during DNA damage Journal Article

Genes Dev, 25 (3), pp. 220-5, 2011, ISSN: 1549-5477 (Electronic) 0890-9369 (Linking).

Links | BibTeX