miR targetome of primary human keratinocytes reveals a function for non-conserved binding sites
miR targetome of primary human keratinocytes reveals a function for non-conserved binding sites
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原代人角质形成细胞的 miR 靶标揭示了非保守结合位点的功能
DOI：
10.1101/2022.07.04.498673
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Thiagarajan L
中科院分区：
文献类型：
--
作者：
Thiagarajan L
人体的稳态由皮肤保护，其中外层中的角质形成细胞分化过程具有关键作用。角质形成细胞基底层增殖的停止和基底层功能的启动在基因转录和信息翻译水平上受到严格控制。mRNA的一个子集在分化过程中必须被抑制，并且已知microRNA通过在3 'UTR处直接结合mRNA而对此做出贡献。利用诱导分化过程中人原代角质形成细胞的RNA测序结果，我们评估了高、中、低表达miR与其靶mRNA的预测结合。我们发现适度表达的miR可以调节更多的mRNA，并且它们使用保守和非保守的典型结合来这样做。大多数抑制的mRNA的累积得分显示与miR的结合令人惊讶地弱，并且我们发现非保守位点对靶标的抑制有显著贡献。虽然至少一个保守位点的存在是miR功能所必需的，但其弱结合可以通过非保守位点来加强。总之，我们发现保守位点和非保守位点的组合降低了miR-mRNA相互作用的结合阈值，从而在细胞分化期间对mRNA靶点进行了更紧密的抑制。
The homeostasis of the human body is protected by the skin, where the process of keratinocyte differentiation in outer layers has a crucial role. Cessation of proliferation in the basal layer of keratinocytes and initiation of their subrabasal functions are tightly controlled at the level of gene transcription and message translation. A subset of mRNAs has to be repressed during differentiation, and microRNAs are known to contribute to this by directly binding mRNAs at the 3’UTRs. Using results of RNA sequencing from human primary keratinocytes during induced differentiation, we evaluated the predicted binding of highly, moderately, and lowly expressed miRs to their target mRNAs. We found that moderately expressed miRs can regulate more mRNAs, and that they do so using both conserved and non-conserved canonical binding. The cumulative score for the majority of repressed mRNAs revealed a surprisingly weak binding to miRs, and we found a significant contribution of non-conserved sites to the repression of the targets. While the presence of at least one conserved site was necessary for the miR function, its weak binding may be reinforced by a non-conserved site. Together, we found that the combination of conserved and non-conserved sites lower the binding threshold for miR-mRNA interactions to assume a tighter repression of the mRNA target during cell differentiation.
影响因子：
14.9
作者：
Kurinna S;Seltmann K;Bachmann AL;Schwendimann A;Thiagarajan L;Hennig P;Beer HD;Mollo MR;Missero C;Werner S
通讯作者：
Werner S
影响因子：
3.9
作者：
Maneesha Aruketty;S. Kurinna
通讯作者：
Maneesha Aruketty;S. Kurinna
DOI：
--
发表时间：
2010
期刊：
--
影响因子：
--
作者：
D. Betel;Anjali J. Koppal;P. Agius;C. Sander;C. Leslie
通讯作者：
D. Betel;Anjali J. Koppal;P. Agius;C. Sander;C. Leslie