ISSN: 1001-0602
EISSN: 1748-7838
2012 impact factor 10.526*
(Thomson Reuters, 2013)
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VOLUME 28 ISSUE 10(10,2018): 981-995

 

The RNA-binding protein ROD1/PTBP3 cotranscriptionally defines AID-loading sites to mediate antibody class switch in mammalian genomes OPEN

 

Juan Chen 1,2, Zhaokui Cai 1,2, Meizhu Bai 3,4, Xiaohua Yu 1,2, Chao Zhang 5, Changchang Cao 1,2, Xihao Hu 1,2, Lei Wang 1,6, Ruibao Su 1,2,Di Wang 1,2, Lei Wang 1,2, Yingpeng Yao 7, Rong Ye 1,2, Baidong Hou 5, Yang Yu1, Shuyang Yu7, Jinsong Li3,4 and Yuanchao Xue1,2

 

1Key Laboratory of RNA Biology, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101 Beijing, China; 2University of Chinese Academy of Sciences, 100049 Beijing, China; 3State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, 320 Yueyang Road, 200031 Shanghai, China; 4School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, 201210 Shanghai, China; 5Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, 100101 Beijing, China; 6College of Life Sciences, Institute for Conservation and Utilization of Agro-bioresources in Dabie Mountains, Xinyang Normal University, 464000 Xinyang, China and 7State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People’s Republic of China

Correspondence:Correspondence: Yuanchao Xue (ycxue@ibp.ac.cn)
These authors contributed equally: Juan Chen, Zhaokui Cai, Meizhu Bai, Xiaohua Yu, Chao Zhang        

 

Activation-induced cytidine deaminase (AID) mediates class switching by binding to a small fraction of single-stranded DNA (ssDNA) to diversify the antibody repertoire. The precise mechanism for highly selective AID targeting in the genome has remained elusive. Here, we report an RNA-binding protein, ROD1 (also known as PTBP3), that is both required and sufficient to define AID-binding sites genome-wide in activated B cells. ROD1 interacts with AID via an ultraconserved loop, which proves to be critical for the recruitment of AID to ssDNA using bi-directionally transcribed nascent RNAs as stepping stones. Strikingly, AID-specific mutations identified in human patients with hyper-IgM syndrome type 2 (HIGM2) completely disrupt the AID interacting surface with ROD1, thereby abolishing the recruitment of AID to immunoglobulin (Ig) loci. Together, our results suggest that bi-directionally transcribed RNA traps the RNA-binding protein ROD1, which serves as a guiding system for AID to load onto specific genomic loci to induce DNA rearrangement during immune responses.

 

https://doi.org/10.1038/s41422-018-0076-9

 
 
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