Journal
NUCLEIC ACIDS RESEARCH
Volume 43, Issue 7, Pages 3712-3725Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkv214
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Funding
- National Special Research Program for Important Infectious Diseases [2013ZX10001004]
- Guangdong Innovative Research Team Program [2009010058]
- National Basic Research Program of China (973 Program) [2010CB912202]
- National Natural Science Foundation of China [30972620]
- Natural Science Foundation of Guangdong [9251008901000022]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20090171110083]
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PIWI-interacting RNA (piRNA) silences the transposons in germlines or induces epigenetic modifications in the invertebrates. However, its function in the mammalian somatic cells remains unknown. Here we demonstrate that a piRNA derived from Growth Arrest Specific 5, a tumor-suppressive long noncoding RNA, potently upregulates the transcription of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a proapoptotic protein, by inducing H3K4 methylation/H3K27 demethylation. Interestingly, the PIWIL1/4 proteins, which bind with this piRNA, directly interact with WDR5, resulting in a site-specific recruitment of the hCOMPASS-like complexes containing at least MLL3 and UTX (KDM6A). We have indicated a novel pathway for piRNAs to specially activate gene expression. Given that MLL3 or UTX are frequently mutated in various tumors, the piRNA/MLL3/UTX complex mediates the induction of TRAIL, and consequently leads to the inhibition of tumor growth.
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