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Activation-induced cytidine deaminase (AID) is localized to subnuclear domains enriched in splicing factors.

Activation-induced cytidine deaminase (AID) is localized to subnuclear domains enriched in splicing factors.

Authors :
Hu, Yi
Ericsson, Ida
Doseth, Berit
Liabakk, Nina B.
Krokan, Hans E.
Kavli, Bodil
Source :
Experimental Cell Research. Mar2014, Vol. 322 Issue 1, p178-192. 15p.
Publication Year :
2014

Abstract

Abstract: Activation-induced cytidine deaminase (AID) is the mutator enzyme in adaptive immunity. AID initiates the antibody diversification processes in activated B cells by deaminating cytosine to uracil in immunoglobulin genes. To some extent other genes are also targeted, which may lead to genome instability and B cell malignancy. Thus, it is crucial to understand its targeting and regulation mechanisms. AID is regulated at several levels including subcellular compartmentalization. However, the complex nuclear distribution and trafficking of AID has not been studied in detail previously. In this work, we examined the subnuclear localization of AID and its interaction partner CTNNBL1 and found that they associate with spliceosome-associated structures including Cajal bodies and nuclear speckles. Moreover, protein kinase A (PKA), which activates AID by phosphorylation at Ser38, is present together with AID in nuclear speckles. Importantly, we demonstrate that AID physically associates with the major spliceosome subunits (small nuclear ribonucleoproteins, snRNPs), as well as other essential splicing components, in addition to the transcription machinery. Based on our findings and the literature, we suggest a transcription-coupled splicing-associated model for AID targeting and activation. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
00144827
Volume :
322
Issue :
1
Database :
Academic Search Index
Journal :
Experimental Cell Research
Publication Type :
Academic Journal
Accession number :
94487589
Full Text :
https://doi.org/10.1016/j.yexcr.2014.01.004