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The long noncoding RNA ROCKI regulates inflammatory gene expression
Author(s) -
Zhang Qiong,
Chao TiChun,
Patil Veena S,
Qin Yue,
Tiwari Shashi Kant,
Chiou Joshua,
Dobin Alexander,
Tsai ChihMing,
Li Zhonghan,
Dang Jason,
Gupta Shagun,
Urdahl Kevin,
Nizet Victor,
Gingeras Thomas R,
Gaulton Kyle J,
Rana Tariq M
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018100041
Subject(s) - biology , gene expression , gene , long non coding rna , rna , microbiology and biotechnology , genetics
Long noncoding RNA s (lnc RNA s) can regulate target gene expression by acting in cis (locally) or in trans (non‐locally). Here, we performed genome‐wide expression analysis of Toll‐like receptor ( TLR )‐stimulated human macrophages to identify pairs of cis ‐acting lnc RNA s and protein‐coding genes involved in innate immunity. A total of 229 gene pairs were identified, many of which were commonly regulated by signaling through multiple TLR s and were involved in the cytokine responses to infection by group B Streptococcus . We focused on elucidating the function of one lnc RNA , named lnc‐ MARCKS or ROCKI (Regulator of Cytokines and Inflammation), which was induced by multiple TLR stimuli and acted as a master regulator of inflammatory responses. ROCKI interacted with APEX 1 (apurinic/apyrimidinic endodeoxyribonuclease 1) to form a ribonucleoprotein complex at the MARCKS promoter. In turn, ROCKI – APEX 1 recruited the histone deacetylase HDAC 1, which removed the H3K27ac modification from the promoter, thus reducing MARCKS transcription and subsequent Ca 2+ signaling and inflammatory gene expression. Finally, genetic variants affecting ROCKI expression were linked to a reduced risk of certain inflammatory and infectious disease in humans, including inflammatory bowel disease and tuberculosis. Collectively, these data highlight the importance of cis ‐acting lnc RNA s in TLR signaling, innate immunity, and pathophysiological inflammation.