Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Sci Adv. 2020 May 15;6(20):eaax3868. doi: 10.1126/sciadv.aax3868. eCollection 2020 May.
Organogenesis is directed by coordinated cell proliferation and differentiation programs. The hierarchical networks of transcription factors driving mammary gland development and function have been widely studied. However, the contribution of posttranscriptional gene expression reprogramming remains largely unexplored. The 3' untranslated regions of messenger RNAs (mRNAs) contain combinatorial ensembles of cis-regulatory elements that define transcript-specific regulation of protein synthesis through their cognate RNA binding proteins. We analyze the contribution of the RNA binding cytoplasmic polyadenylation element-binding (CPEB) protein family, which collectively regulate mRNA translation for about 30% of the genome. We find that CPEB2 is required for the integration of hormonal signaling by controlling the protein expression from a subset of ER/PR- regulated transcripts. Furthermore, CPEB2 is critical for the development of ER-positive breast tumors. This work uncovers a previously unknown gene expression regulation level in breast morphogenesis and tumorigenesis, coordinating sequential transcriptional and posttranscriptional layers of gene expression regulation.
器官发生是由协调的细胞增殖和分化程序所指导的。 驱动乳腺发育和功能的转录因子层次网络已经得到了广泛的研究。 然而，转录后基因表达重编程的贡献在很大程度上仍未得到探索。信使 RNA（mRNA）的 3'非翻译区包含组合的顺式调控元件，通过其同源 RNA 结合蛋白定义蛋白质合成的转录特异性调节。 我们分析了 RNA 结合细胞质多聚腺苷酸化元件结合（CPEB）蛋白家族的贡献，该家族共同调节基因组中约 30%的 mRNA 翻译。 我们发现 CPEB2 通过控制一组 ER/PR 调节转录本的蛋白质表达，是激素信号整合所必需的。 此外，CPEB2 对于 ER 阳性乳腺癌的发展至关重要。 这项工作揭示了乳腺形态发生和肿瘤发生中以前未知的基因表达调控水平，协调了基因表达调控的顺序转录和转录后层。
