S.Millevoi

  RNA binding proteins and post-transcriptional regulation in cancer

 

 

 

 

 

 

 

Our research project at a glance
Post-transcriptional expression of genes is deregulated in cancer leading to disruption of protein biosynthesis programs responsible for tumor progression and resistance to therapies. Our research program brings together clinicians, biologists and biostatistics experts to uncover the orchestration of translational regulation molecular mechanisms controlled by RNA-binding proteins in cancer cells and their impact on patient fate.
Objectives
Altered post-transcrip-tional gene expression is a feature of cancer. RNA binding proteins (Rbps) are major regulators of post-transcriptional processes, including splicing and polyadeneylation of pre-RNA, stability and mRNA translation. These factors provide dynamic control of the post-transcriptional expression of genes under normal conditions as well as under various stresses, thus contributing to deregulations of RNA metabolism in cancer cells. They can also impact genomic instability by establishing a direct link between DNA and RNA processes. Rbps recognize specific elements of sequences and structures. Of these, G-quadruplex Rnas have been shown to affect post-transcriptional expression of genes involved in cancer.
Our research focuses on understanding the role of Rbps in reprogramming the post-transcriptional expression of genes in response to stress as well as the deregulations associated with cancer pathology.

Our objectives are to:

  • provide a mechanistic and functional understanding of the impact of Rbps in the development, progression and treatment of cancer,
  • improve knowledge on the regulation of G-quadruplex RNA and its targeting in cancer cells,
  • explore the emerging concept that proteins from DNA damage, in addition to their role on DNA and signalling, target mRNA to
  • regulate post-transcriptional gene expression.
Key words
  • post-transcriptional expression of genes mRNA
  • RNA binding proteins
  • Translation of the mRNAs
  • Response to DNA damage
  • G-quadruplex RNA structures
Grants and funders
  • National Institute of Health and Medical Research
  • National Research Agency
  • ARC Foundation for Cancer Research
  • National League Against Cancer
  • Occitania region Pyrenees – Mediterranean
  • Campus France
  • Cancéropôle Great Southwest
  • Canadian Institutes of Health Research

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).

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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).

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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).

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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).

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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