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 Egr1 on miR-125a-3p efficiency. Further experiments revealed that deleting sequence 97-227aa containing dsRBD B domain of TRBP eliminated the binding phenomenon between Egr1 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.
Department of Clinical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Junxia
J
Wei
Department of Clinical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Yongri
Y
Ouyang
Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
Xia
X
Li
Department of Ophthalmology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Baoyi
B
Zhu
Department of Nephroloogy, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Jie
J
Yang
Department of Clinical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Ying
Y
Cui
Department of Clinical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Xi
X
Chen
Department of Clinical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Fang
F
Lin
Department of Clinical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Min
M
Long
Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
Angang
A
Yang
Department of Clinical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: tdzhz328@aliyun.com.
Ke
K
Dong
Department of Clinical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Huizhong
H
Zhang
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D004330:Drosophila; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D000099253:Trans-Activation Responsive RNA-Binding Protein
D051766:Early Growth Response Protein 1; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000099253:Trans-Activation Responsive RNA-Binding Protein; C497325:EGR1 protein, human; C531888:MIRN125 microRNA, human; C471146:bantam microRNA, Drosophila
Egr1; RISC; TRBP; miR-125a-3p