A double-negative feedback loop mediated by non-coding RNAs contributes to tooth morphogenesis

IF 3.9 4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology
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Abstract

Tooth morphogenesis is a critically ordered process manipulated by a range of signaling factors. Particularly, the involvement of fine-tuned signaling mediated by non-coding RNAs has been of longstanding interest. Here, we revealed a double-negative feedback loop acted by a long non-coding RNA (LOC102159588) and a microRNA (miR-133b) that modulated tooth morphogenesis of miniature swine. Mechanistically, miR-133b repressed the transcription of LOC102159588 through downstream target Sp1. Conversely, LOC102159588 not only inhibited the transport of pre-miR-133b from the nucleus to the cytoplasm by regulating exportin-5 but also served as a sponge in the cytoplasm, suppressing functional miR-133b. Together, the double-negative feedback loop maintained normal tooth morphogenesis by modulating endogenous apoptosis. Related disruptions would lead to an arrest of tooth development and may result in tooth malformations.

Abstract Image

非编码 RNA 介导的双负反馈环有助于牙齿的形态发生。
牙齿的形态发生是一个关键的有序过程,受到一系列信号因子的操纵。特别是,由非编码 RNA 介导的微调信号的参与一直备受关注。在这里,我们揭示了一个由长非编码 RNA(LOC102159588)和 microRNA(miR-133b)作用的双负反馈环,它调控了微型猪的牙齿形态发生。从机制上讲,miR-133b 通过下游靶标 Sp1 抑制 LOC102159588 的转录。相反,LOC102159588 不仅通过调节 exportin-5 抑制前 miR-133b 从细胞核向细胞质的转运,还在细胞质中充当海绵,抑制功能性 miR-133b。双重负反馈环共同通过调节内源性凋亡来维持正常的牙齿形态发生。相关的干扰会导致牙齿发育停滞,并可能导致牙齿畸形。
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来源期刊
Cells and Development
Cells and Development Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
2.90
自引率
0.00%
发文量
33
审稿时长
41 days
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