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Mutual induction of transcription factor PPAR γ and micro RNA s miR‐145 and miR‐329
Author(s) -
Dharap Ashutosh,
Pokrzywa Courtney,
Murali Shruthi,
Kaimal Balarama,
Vemuganti Raghu
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13220
Subject(s) - promoter , microrna , transcription factor , peroxisome proliferator activated receptor , biology , response element , microbiology and biotechnology , transcription (linguistics) , gene , gene expression , genetics , linguistics , philosophy
Micro RNA s (mi RNA s) are small non‐coding RNA s that are known to control mRNA translation. Most mi RNA s are transcribed from specific genes with well‐defined promoters located throughout the genome. The mechanisms that control mi RNA expression under normal and pathological conditions are not yet understood clearly. Peroxisome proliferator‐activated receptor ( PPAR ) γ is a ligand‐activated transcription factor that is extensively distributed in the CNS . PPAR γ activation induces neuroprotection by modulating genes that contain peroxisome proliferator response elements ( PPRE s) in their promoters. We presently evaluated if PPAR γ modulates mi RNA expression. When adult rats were treated with PPAR γ agonist rosiglitazone, expression of 28 mi RNA s altered significantly (12 up‐ and 16 down‐regulated; 3–119 fold) in the cerebral cortex compared to vehicle‐treated controls. In silico analysis showed 1–5 PPRE s in the putative promoter regions (within 1 Kb upstream of the transcription start site) of these mi RNA genes. Cotransfection with a PPAR γ constitutively expressing vector significantly induced the miR‐145 and miR‐329 promoter vectors (each have four PPRE s), which was curtailed by point mutations of PPRE s in their promoters. Interestingly, the PPAR γ promoter has binding sites for both these mi RNA s and transfection with miR‐329 mimic and miR‐145 mimic induced the PPAR γ expression. Thus, these studies show a cyclical induction of mi RNA s and PPAR γ, indicating that the pleiotropic beneficial effects of PPAR γ agonists might be modulated in part by mi RNA s and their down‐stream mRNA s.We proposed that promoters of many microRNAs contain the binding sites for the transcription factor PPARγ. Activation of PPARγ modulates the expression of these microRNAs. Two such PPARγ‐responsive microRNAs (miR‐145 and miR‐329) bind to PPARγ promoter to induce its expression. This indicates the presence of a feedback loop by which transcription factors and microRNAs can modulate each other.