Deletion of AU-rich elements within the Bcl2 3'UTR reduces protein expression and B cell survival in vivo.
Díaz-Muñoz, Manuel D
Bell, Sarah E
Public Library of Science (PLoS)
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Díaz-Muñoz, M. D., Bell, S. E., & Turner, M. (2015). Deletion of AU-rich elements within the Bcl2 3'UTR reduces protein expression and B cell survival in vivo.. PLoS One, 10 (2), e0116899. https://doi.org/10.1371/journal.pone.0116899
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.
B-Lymphocytes, Animals, Mice, Heterogeneous-Nuclear Ribonucleoprotein D, Proto-Oncogene Proteins c-bcl-2, Cell Survival, Gene Expression Regulation, Sequence Deletion, Base Sequence, RNA Stability, AU Rich Elements, ELAV-Like Protein 1, Heterogeneous Nuclear Ribonucleoprotein D0
External DOI: https://doi.org/10.1371/journal.pone.0116899
This record's URL: https://www.repository.cam.ac.uk/handle/1810/293909
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/