Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.25.1 (
deoxyribonuclease
)
1,471
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Long noncoding RNAs (lncRNAs) 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 lncRNAs 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 TLRs and were involved in the cytokine responses to infection by group B
Streptococcus
We focused on elucidating the function of one lncRNA, 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 APEX1 (apurinic/apyrimidinic
endodeoxyribonuclease
1) to form a ribonucleoprotein complex at the
MARCKS
promoter. In turn,
ROCKI
-APEX1 recruited the histone deacetylase HDAC1, 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 lncRNAs in TLR signaling, innate immunity, and pathophysiological inflammation.
...
PMID:The long noncoding RNA
ROCKI
regulates inflammatory gene expression. 3091 8
