Deletion of the RNA-binding proteins Zfp36l1 and Zfp36l2 leads to perturbed thymic development and T-lymphoblastic leukaemia.

Martin Turner (1) , Daniel James Hodson (1) , Michelle Louise Janas (1) , Alison Galloway (1) , Simon Andrews (1) , Cheuk Li (1) , Richard Pannell (1) , Christian William Siebel (1) , Hugh Robson Macdonald (1) , Kim de Keersmaecker (1) , Adolfo A Ferrando (1) , Gerald Georg Grütz (1) , Sarah Bell (1)

1 Laboratory of Lymphocyte Signaling and Development

ZFP36L1 and ZFP36L2 are RNA-binding proteins (RBPs) which interact with AU-rich elements in the 3'UTR of mRNA, leading to mRNA degradation and translational repression. Mice lacking ZFP36L1 and ZFP36L2 during thymopoiesis develop a Notch1-dependent T cell acute lymphoblastic leukaemia (T-ALL). Prior to the onset of T-ALL, thymic development is perturbed with accumulation of cells which have passed through the β-selection checkpoint without first expressing T cell receptorβ (TCRβ). Notch1 expression is increased in non-transformed thymocytes in the absence of ZFP36L1 and ZFP36L2. Both RBPs interact with evolutionarily conserved AU-rich elements within the 3' untranslated region of Notch1 and suppress its expression. These data establish a role for ZFP36L1 and ZFP36L2 during thymocyte development and in the prevention of malignant transformation.

Mots clés: Development; Gene regulation; T cells

Martin Turner, Daniel James Hodson, Michelle Louise Janas, Alison Galloway, Simon Andrews, et al.. Deletion of the RNA-binding proteins Zfp36l1 and Zfp36l2 leads to perturbed thymic development and T-lymphoblastic leukaemia.. Nature Immunology, 2010, ⟨10.1038/ni.1901⟩. ⟨hal-00554655⟩