title: Deletion of AU-rich elements within the Bcl2 3'UTR reduces protein expression and B cell survival in vivo.
abstract: Post-transcriptional mRNA regulation by RNA binding proteins (RBPs) associated with AU-rich elements (AREs) present in the 3' untranslated region (3'UTR) of specific mRNAs modulates transcript stability and translation in eukaryotic cells. Here we have functionally characterised the importance of the AREs present within the Bcl2 3'UTR in order to maintain Bcl2 expression. Gene targeting deletion of 300 nucleotides of the Bcl2 3'UTR rich in AREs diminishes Bcl2 mRNA stability and protein levels in primary B cells, decreasing cell lifespan. Generation of chimeric mice indicates that Bcl2-ARE∆/∆ B cells have an intrinsic competitive disadvantage compared to wild type cells. Biochemical assays and predictions using a bioinformatics approach show that several RBPs bind to the Bcl2 AREs, including AUF1 and HuR proteins. Altogether, association of RBPs to Bcl2 AREs contributes to Bcl2 protein expression by stabilizing Bcl2 mRNA and promotes B cell maintenance.
authors: Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.
authors: Manuel D
authors: MD
authors: Díaz-Muñoz
authors: Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.
authors: Sarah E
authors: SE
authors: Bell
authors: Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.
authors: Martin
authors: M
authors: Turner
mesh_terms: D063307:AU Rich Elements / Q000235:genetics*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D002470:Cell Survival / Q000235:genetics; D000067780:ELAV-Like Protein 1 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D020871:RNA Stability; D017384:Sequence Deletion
chemical_list: D000067780:ELAV-Like Protein 1; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse