Repository logo
 

Deletion of AU-rich elements within the Bcl2 3'UTR reduces protein expression and B cell survival in vivo.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Díaz-Muñoz, Manuel D 
Bell, Sarah E 

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.

Description

Keywords

AU Rich Elements, Animals, B-Lymphocytes, Base Sequence, Cell Survival, ELAV-Like Protein 1, Gene Expression Regulation, Heterogeneous Nuclear Ribonucleoprotein D0, Heterogeneous-Nuclear Ribonucleoprotein D, Mice, Proto-Oncogene Proteins c-bcl-2, RNA Stability, Sequence Deletion

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

10

Publisher

Public Library of Science (PLoS)