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http://dx.doi.org/10.14348/molcells.2022.2158

Hsa-miR-422a Originated from Short Interspersed Nuclear Element Increases ARID5B Expression by Collaborating with NF-E2  

Kim, Woo Ryung (Department of Integrated Biological Science, Pusan National University)
Park, Eun Gyung (Department of Integrated Biological Science, Pusan National University)
Lee, Hee-Eun (National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Park, Sang-Je (National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Huh, Jae-Won (National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Kim, Jeong Nam (Department of Microbiology, College of Natural Sciences, Pusan National University)
Kim, Heui-Soo (Institute of Systems Biology, Pusan National University)
Abstract
MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate the expression of target messenger RNA (mRNA) complementary to the 3' untranslated region (UTR) at the post-transcriptional level. Hsa-miR-422a, which is commonly known as miRNA derived from transposable element (MDTE), was derived from short interspersed nuclear element (SINE). Through expression analysis, hsa-miR-422a was found to be highly expressed in both the small intestine and liver of crab-eating monkey. AT-Rich Interaction Domain 5 B (ARID5B) was selected as the target gene of hsa-miR-422a, which has two binding sites in both the exon and 3'UTR of ARID5B. To identify the interaction between hsa-miR-422a and ARID5B, a dual luciferase assay was conducted in HepG2 cell line. The luciferase activity of cells treated with the hsa-miR-422a mimic was upregulated and inversely downregulated when both the hsa-miR-422a mimic and inhibitor were administered. Nuclear factor erythroid-2 (NF-E2) was selected as the core transcription factor (TF) via feed forward loop analysis. The luciferase expression was downregulated when both the hsa-miR-422a mimic and siRNA of NF-E2 were treated, compared to the treatment of the hsa-miR-422a mimic alone. The present study suggests that hsa-miR-422a derived from SINE could bind to the exon region as well as the 3'UTR of ARID5B. Additionally, hsa-miR-422a was found to share binding sites in ARID5B with several TFs, including NF-E2. The hsa-miR-422a might thus interact with TF to regulate the expression of ARID5B, as demonstrated experimentally. Altogether, hsa-miR-422a acts as a super enhancer miRNA of ARID5B by collaborating with TF and NF-E2.
Keywords
crab-eating monkey; microRNA-422a; nuclear factor erythroid-2; short interspersed nuclear element; transposable element;
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