1. Nuclear receptor RXRα binds the precursor of miR-103 to inhibit its maturation.
- Author
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Ye X, Yang Y, Yao J, Wang M, Liu Y, Xie G, Zeng Z, Zhang XK, and Zhou H
- Subjects
- Transcription Factors, Argonaute Proteins, Receptors, Cytoplasmic and Nuclear, MicroRNAs genetics
- Abstract
Background: The maturation of microRNAs (miRNAs) successively undergoes Drosha, Dicer, and Argonaute -mediated processing, however, the intricate regulations of the individual miRNA maturation are largely unknown. Retinoid x receptor alpha (RXRα) belongs to nuclear receptors that regulate gene transcription by binding to DNA elements, however, whether RXRα binds to miRNAs to exert physiological functions is not known., Results: In this work, we found that RXRα directly binds to the precursor of miR-103 (pre-miR-103a-2) via its DNA-binding domain with a preferred binding sequence of AGGUCA. The binding of RXRα inhibits the processing of miR-103 maturation from pre-miR-103a-2. Mechanistically, RXRα prevents the nuclear export of pre-miR-103a-2 for further processing by inhibiting the association of exportin-5 with pre-miR-103a-2. Pathophysiologically, the negative effect of RXRα on miR-103 maturation correlates to the positive effects of RXRα on the expression of Dicer, a target of miR-103, and on the inhibition of breast cancer., Conclusions: Our findings unravel an unexpected role of transcription factor RXRα in specific miRNA maturation at post-transcriptional level through pre-miRNA binding, and present a mechanistic insight regarding RXRα role in breast cancer progression., (© 2023. BioMed Central Ltd., part of Springer Nature.)
- Published
- 2023
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