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

doi:10.1038/s41422-018-0076-9

	The RNA-binding protein ROD1/PTBP3 cotranscriptionally defines AID-loading sites to mediate antibody class switch in mammalian genomes
	Chen, Juan 1,2; Cai, Zhaokui 1,2; Bai, Meizhu3,4,5 ; Yu, Xiaohua 1,2; Zhang, Chao 6; Cao, Changchang 1,2; Hu, Xihao 1,2; Wang, Lei 1,2,7; Su, Ruibao 1,2; Wang, Di 1,2; Yao, Yingpeng 8; Ye, Rong 1,2; Hou, Baidong 6; Yu, Yang 1; Yu, Shuyang 8; Li, Jinsong3,4,5 ; Xue, Yuanchao 1,2
	2018-10
发表期刊	CELL RESEARCH (IF:28.1[JCR-2023],36.4[5-Year])
ISSN	1001-0602
卷号	28 期号:10 页码:981-995
发表状态	已发表
DOI	10.1038/s41422-018-0076-9
摘要	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 AD 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.
收录类别	SCI ; SCIE ; CSCD
语种	英语
资助项目	Chinese Academy of Sciences[XDB19010203]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000446172500005
CSCD记录号	CSCD:6366205
出版者	INST BIOCHEMISTRY & CELL BIOLOGY
WOS关键词	SINGLE-STRANDED-DNA ; CYTIDINE DEAMINASE AID ; ONE-STEP GENERATION ; SOMATIC HYPERMUTATION ; SEQUENCING REVEALS ; B-CELLS ; SUPER-ENHANCERS ; READ ALIGNMENT ; RECRUIT AID ; TARGETS AID
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/28069
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_李劲松组
通讯作者	Xue, Yuanchao
作者单位	1.Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Key Lab RNA Biol, Beijing 100101, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Key Lab Mol Androl, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol,Shanghai Inst Biochem & Ce, 320 Yueyang Rd, Shanghai 200031, Peoples R China 4.Univ Chinese Acad Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 6.Chinese Acad Sci, Inst Biophys, Key Lab Infect & Immun, Beijing 100101, Peoples R China 7.Xinyang Normal Univ, Coll Life Sci, Inst Conservat & Utilizat Agrobioresources Dabie, Xinyang 464000, Peoples R China 8.China Agr Univ, Coll Biol Sci, State Key Lab Agrobiotechnol, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Chen, Juan,Cai, Zhaokui,Bai, Meizhu,et al. The RNA-binding protein ROD1/PTBP3 cotranscriptionally defines AID-loading sites to mediate antibody class switch in mammalian genomes[J]. CELL RESEARCH,2018,28(10):981-995.
APA	Chen, Juan.,Cai, Zhaokui.,Bai, Meizhu.,Yu, Xiaohua.,Zhang, Chao.,...&Xue, Yuanchao.(2018).The RNA-binding protein ROD1/PTBP3 cotranscriptionally defines AID-loading sites to mediate antibody class switch in mammalian genomes.CELL RESEARCH,28(10),981-995.
MLA	Chen, Juan,et al."The RNA-binding protein ROD1/PTBP3 cotranscriptionally defines AID-loading sites to mediate antibody class switch in mammalian genomes".CELL RESEARCH 28.10(2018):981-995.