Early growth response gene 1, a TRBP binding protein, is involved in miRNA activity of miR-125a-3p in human cells

Background: MicroRNAs (miRNAs) are key regulators of many cellular pathways. However, the picture for components or regulators involved in the process of miRNA biogenesis and function remains to be further elucidated. Early growth response gene 1 (Egr1) has long been considered as tumor suppressor and transcriptional factor involved in cell proliferation and regulation of apoptosis. Results: Here we show that Egr1 is able to modulate guide strand loading of certain miRNAs or siRNAs in human HEK293 and A549 cells, which is related with thermodynamic parameters of miRNA or siRNA. Further, we found that Egr1 modulates the silencing activity of miR-125a-3p in vivo. Immunoprecipitation experiment demonstrated that Egr1 could bind miRNA biogenesis protein TAR RNA- binding protein2 (TRBP2), and knockdown TRBP by RNAi abolished the regulating effects of Egrl on miR-125a-3p efficiency. Further experiments revealed that deleting sequence 97-227aa containing dsRBD B domain of TRBP eliminated the binding phenomenon between Egrl and TRBP and impaired the effect of Egr1 on miR-125a-3p efficiency. Conclusions: Taken together, our study has demonstrated that Egr1 is able to regulate miRNA activity of miR-125a-3p in human cells through binding TRBP, which highlights an unexpected function of Egr1 in miRNA pathway. (C) 2015 Elsevier Inc. All rights reserved.