A Long Noncoding RNA Mediates Both Activation and Repression of Immune Response Genes

被引：1143

作者：

Carpenter, Susan ^{[1
,2
]}

Aiello, Daniel ^{[1
]}

Atianand, Maninjay K. ^{[1
]}

Ricci, Emiliano P. ^{[3
]}

Gandhi, Pallavi ^{[1
]}

Hall, Lisa L. ^{[4
]}

Byron, Meg ^{[4
]}

Monks, Brian ^{[1
]}

Henry-Bezy, Meabh ^{[1
]}

Lawrence, Jeanne B. ^{[4
]}

O'Neill, Luke A. J. ^{[2
]}

Moore, Melissa J. ^{[3
]}

Caffrey, Daniel R. ^{[1
]}

Fitzgerald, Katherine A. ^{[1
]}

机构：

[1] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA

[2] Trinity Coll Dublin, Sch Biochem & Immunol, Dublin 2, Ireland

[3] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA

[4] Univ Massachusetts, Sch Med, Dept Cell & Dev Biol, Worcester, MA 01605 USA

来源：

SCIENCE | 2013年 / 341卷 / 6147期

关键词：

IN-VIVO; EXPRESSION; REVEALS; GENOME; CELLS; A/B; TRANSCRIPTOMES; OSTEOPONTIN; TRANSLATION; RESOLUTION;

D O I：

10.1126/science.1240925

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

An inducible program of inflammatory gene expression is central to antimicrobial defenses. This response is controlled by a collaboration involving signal-dependent activation of transcription factors, transcriptional co-regulators, and chromatin-modifying factors. We have identified a long noncoding RNA (lncRNA) that acts as a key regulator of this inflammatory response. Pattern recognition receptors such as the Toll-like receptors induce the expression of numerous lncRNAs. One of these, lincRNA-Cox2, mediates both the activation and repression of distinct classes of immune genes. Transcriptional repression of target genes is dependent on interactions of lincRNA-Cox2 with heterogeneous nuclear ribonucleoprotein A/B and A2/B1. Collectively, these studies unveil a central role of lincRNA-Cox2 as a broad-acting regulatory component of the circuit that controls the inflammatory response.

引用

页码：789 / 792

页数：4

共 28 条

[1]

Transcript Dynamics of Proinflammatory Genes Revealed by Sequence Analysis of Subcellular RNA Fractions [J].

Bhatt, Dev M. ;

Pandya-Jones, Amy ;

Tong, Ann-Jay ;

Barozzi, Iros ;

Lissner, Michelle M. ;

Natoli, Gioacchino ;

Black, Douglas L. ;

Smale, Stephen T. .

CELL, 2012, 150 (02) :279-290

[2]

Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].

Birney, Ewan ;

Stamatoyannopoulos, John A. ;

Dutta, Anindya ;

Guigo, Roderic ;

Gingeras, Thomas R. ;

Margulies, Elliott H. ;

Weng, Zhiping ;

Snyder, Michael ;

Dermitzakis, Emmanouil T. ;

Stamatoyannopoulos, John A. ;

Thurman, Robert E. ;

Kuehn, Michael S. ;

Taylor, Christopher M. ;

Neph, Shane ;

Koch, Christoph M. ;

Asthana, Saurabh ;

Malhotra, Ankit ;

Adzhubei, Ivan ;

Greenbaum, Jason A. ;

Andrews, Robert M. ;

Flicek, Paul ;

Boyle, Patrick J. ;

Cao, Hua ;

Carter, Nigel P. ;

Clelland, Gayle K. ;

Davis, Sean ;

Day, Nathan ;

Dhami, Pawandeep ;

Dillon, Shane C. ;

Dorschner, Michael O. ;

Fiegler, Heike ;

Giresi, Paul G. ;

Goldy, Jeff ;

Hawrylycz, Michael ;

Haydock, Andrew ;

Humbert, Richard ;

James, Keith D. ;

Johnson, Brett E. ;

Johnson, Ericka M. ;

Frum, Tristan T. ;

Rosenzweig, Elizabeth R. ;

Karnani, Neerja ;

Lee, Kirsten ;

Lefebvre, Gregory C. ;

Navas, Patrick A. ;

Neri, Fidencio ;

Parker, Stephen C. J. ;

Sabo, Peter J. ;

Sandstrom, Richard ;

Shafer, Anthony .

NATURE, 2007, 447 (7146) :799-816

[3]

Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution [J].

Cheng, J ;

Kapranov, P ;

Drenkow, J ;

Dike, S ;

Brubaker, S ;

Patel, S ;

Long, J ;

Stern, D ;

Tammana, H ;

Helt, G ;

Sementchenko, V ;

Piccolboni, A ;

Bekiranov, S ;

Bailey, DK ;

Ganesh, M ;

Ghosh, S ;

Bell, I ;

Gerhard, DS ;

Gingeras, TR .

SCIENCE, 2005, 308 (5725) :1149-1154

[4]

Cutting Edge: Influence of Tmevpg1, a Long Intergenic Noncoding RNA, on the Expression of Ifng by Th1 Cells [J].

Collier, Sarah P. ;

Collins, Patrick L. ;

Williams, Christopher L. ;

Boothby, Mark R. ;

Aune, Thomas M. .

JOURNAL OF IMMUNOLOGY, 2012, 189 (05) :2084-2088

[5]

From transcript to protein [J].

Dreyfuss, G ;

Hentze, M ;

Lamond, AI .

CELL, 1996, 85 (07) :963-972

[6]

Transcriptional regulatory functions of heterogeneous nuclear ribonucleoproteim-U and -A/B in endotoxin-mediated macrophage expression of osteopontin [J].

Gao, CJ ;

Guo, HT ;

Mi, ZY ;

Wai, PY ;

Kuo, PC .

JOURNAL OF IMMUNOLOGY, 2005, 175 (01) :523-530

[7]

S-nitrosylation of heterogeneous nuclear ribonucleoprotein A/B regulates osteopontin transcription in endotoxin-stimulated murine macrophages [J].

Gao, CJ ;

Guo, HT ;

Wei, JP ;

Mi, ZY ;

Wai, P ;

Kuo, PC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (12) :11236-11243

[8]

The NeST Long ncRNA Controls Microbial Susceptibility and Epigenetic Activation of the Interferon-γ Locus [J].

Gomez, J. Antonio ;

Wapinski, Orly L. ;

Yang, Yul W. ;

Bureau, Jean-Francois ;

Gopinath, Smita ;

Monack, Denise M. ;

Chang, Howard Y. ;

Brahic, Michel ;

Kirkegaard, Karla .

CELL, 2013, 152 (04) :743-754

[9]

Modular regulatory principles of large non-coding RNAs [J].

Guttman, Mitchell ;

Rinn, John L. .

NATURE, 2012, 482 (7385) :339-346

[10]

Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs [J].

Guttman, Mitchell ;

Garber, Manuel ;

Levin, Joshua Z. ;

Donaghey, Julie ;

Robinson, James ;

Adiconis, Xian ;

Fan, Lin ;

Koziol, Magdalena J. ;

Gnirke, Andreas ;

Nusbaum, Chad ;

Rinn, John L. ;

Lander, Eric S. ;

Regev, Aviv .

NATURE BIOTECHNOLOGY, 2010, 28 (05) :503-U166

← 1 2 3 →