Dynamic MicroRNA Gene Transcription and Processing during T Cell Development

被引:69
作者
Kirigin, Francis F. [2 ,3 ]
Lindstedt, Kenneth [1 ]
Sellars, Maclean [2 ]
Ciofani, Maria [2 ]
Low, Siao Li [1 ]
Jones, Lachlan [1 ]
Bell, Fiona [1 ]
Pauli, Florencia [4 ]
Bonneau, Richard [3 ]
Myers, Richard M. [4 ,5 ]
Littman, Dan R. [2 ,6 ]
Chong, Mark M. W. [1 ,7 ]
机构
[1] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia
[2] NYU, Sch Med, Kimmel Ctr Biol & Med, Skirball Inst Biomol Med, New York, NY 10016 USA
[3] NYU, Ctr Genom & Syst Biol, New York, NY 10003 USA
[4] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA
[5] Courant Inst Math Sci, New York, NY 10003 USA
[6] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA
[7] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia
基金
美国国家科学基金会; 美国国家卫生研究院; 英国医学研究理事会;
关键词
NONCODING RNAS; POLYMERASE-II; HUMAN GENOME; IDENTIFICATION; BIOGENESIS; EXPRESSION; PROMOTERS; SEQUENCES; SELECTION; MIR-181A;
D O I
10.4049/jimmunol.1103175
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
By disrupting microRNA (miRNA) biogenesis, we previously showed that this pathway is critical for the differentiation and function of T cells. Although various cloning studies have shown that many miRNAs are expressed during T cell development, and in a dynamic manner, it was unclear how comprehensive these earlier analyses were. We therefore decided to profile miRNA expression by next generation sequencing. Furthermore, we profiled miRNA expression starting from the hematopoietic stem cell. This analysis revealed that miRNA expression during T cell development is extremely dynamic, with 645 miRNAs sequenced, and the expression of some varying by as much as 3 orders of magnitude. Furthermore, changes in precursor processing led to altered mature miRNA sequences. We also analyzed the structures of the primary miRNA transcripts expressed in T cells and found that many were extremely long. The longest was pri-mir-29b-1/29a at similar to 168 kb. All the long pri-miRNAs also displayed extensive splicing. Our findings indicate that miRNA expression during T cell development is both a highly dynamic and a highly regulated process. The Journal of Immunology, 2012, 188: 3257-3267.
引用
收藏
页码:3257 / 3267
页数:11
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