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- Title
Nuclear receptor RXRα binds the precursor of miR-103 to inhibit its maturation.
- Authors
Ye, Xiaohong; Yang, Yun; Yao, Jiayue; Wang, Mo; Liu, Yixin; Xie, Guobin; Zeng, Zhiping; Zhang, Xiao-kun; Zhou, Hu
- 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.
- Subjects
RETINOID X receptors; RNA regulation; TRANSCRIPTION factors; BREAST cancer; CANCER invasiveness
- Publication
BMC Biology, 2023, Vol 21, Issue 1, p1
- ISSN
1741-7007
- Publication type
Article
- DOI
10.1186/s12915-023-01701-3