Quantitative and time-resolved miRNA pattern of early human T cell activation

被引：18

作者：

Diener, Caroline ^{[1
]}

Hart, Martin ^{[1
]}

Kehl, Tim ^{[2
]}

Rheinheimer, Stefanie ^{[1
]}

Ludwig, Nicole ^{[1
]}

Krammes, Lena ^{[1
]}

Pawusch, Sarah ^{[1
]}

Lenhof, Kerstin ^{[2
]}

Taenzer, Tanja ^{[3
,4
]}

Schub, David ^{[5
]}

Sester, Martina ^{[5
]}

Walch-Rueckheim, Barbara ^{[3
,4
]}

Keller, Andreas ^{[6
,7
]}

Lenhof, Hans-Peter ^{[2
]}

Meese, Eckart ^{[1
]}

机构：

[1] Saarland Univ, Inst Human Genet, D-66421 Homburg, Germany

[2] Saarland Univ, Ctr Bioinformat, Saarland Informat Campus, D-66123 Saarbrucken, Germany

[3] Saarland Univ, Inst Virol, D-66421 Homburg, Germany

[4] Saarland Univ, Ctr Human & Mol Biol, D-66421 Homburg, Germany

[5] Saarland Univ, Dept Transplant & Infect Immunol, D-66421 Homburg, Germany

[6] Saarland Univ, Chair Clin Bioinformat, D-66123 Saarbrucken, Germany

[7] Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA 94305 USA

来源：

NUCLEIC ACIDS RESEARCH | 2020年 / 48卷 / 18期

关键词：

FALSE DISCOVERY RATE; GENE-EXPRESSION; MESSENGER-RNAS; IN-VITRO; MICRORNA; PROTEIN; PROLIFERATION; ARGONAUTE; RECEPTOR; TARGETS;

D O I：

10.1093/nar/gkaa788

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

T cells are central to the immune response against various pathogens and cancer cells. Complex networks of transcriptional and post-transcriptional regulators, including microRNAs (miRNAs), coordinate the T cell activation process. Available miRNA datasets, however, do not sufficiently dissolve the dynamic changes of miRNA controlled networks upon T cell activation. Here, we established a quantitative and time-resolved expression pattern for the entire miRNome over a period of 24 h upon human T-cell activation. Based on our time-resolved datasets, we identified central miRNAs and specified common miRNA expression profiles. We found the most prominent quantitative expression changes for miR-155-5p with a range from initially 40 molecules/cell to 1600 molecules/cell upon T-cell activation. We established a comprehensive dynamic regulatory network of both the up- and downstream regulation of miR-155. Upstream, we highlight IRF4 and its complexes with SPI1 and BATF as central for the transcriptional regulation of miR-155. Downstream of miR-155-5p, we verified 17 of its target genes by the time-resolved data recorded after T cell activation. Our data provide comprehensive insights into the range of stimulus induced miRNA abundance changes and lay the ground to identify efficient points of intervention for modifying the T cell response.

引用

页码：10164 / 10183

页数：20

共 106 条

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