Deletion of AU-rich elements within the Bcl2 3'UTR reduces protein expression and B cell survival in vivo.
Deletion of AU-rich elements within the Bcl2 3'UTR reduces protein expression and B cell survival in vivo.
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DOI:
10.1371/journal.pone.0116899
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Turner M
中科院分区:
文献类型:
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作者:
Díaz-Muñoz MD;Bell SE;Turner M
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.
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影响因子:
32.4
作者:
Kontoyiannis, D;Pasparakis, M;Kollias, G
通讯作者:
Kollias, G
DOI:
10.1093/bioinformatics/btt495
发表时间:
2013-11-15
期刊:
Bioinformatics (Oxford, England)
影响因子:
--
作者:
Agostini F;Zanzoni A;Klus P;Marchese D;Cirillo D;Tartaglia GG
通讯作者:
Tartaglia GG
影响因子:
16
作者:
Mukherjee N;Corcoran DL;Nusbaum JD;Reid DW;Georgiev S;Hafner M;Ascano M Jr;Tuschl T;Ohler U;Keene JD
通讯作者:
Keene JD
影响因子:
20.3
作者:
Houzet, L;Morello, D;Kruys, V
通讯作者:
Kruys, V
影响因子:
16.8
作者:
通讯作者:
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