College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310030, P. R. China.
MOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310030, China.
J Agric Food Chem. 2024 Mar 27;72(12):6414-6423. doi: 10.1021/acs.jafc.4c00580. Epub 2024 Mar 19.
Previous research has demonstrated that in pregnant mice deficient in l-methionine (Met), the mixture of the dipeptide l-methionyl-l-methionine (Met-Met) with Met was more effective than Met alone in promoting mammogenesis and lactogenesis. This study aimed to investigate the role of a novel long noncoding RNA (lncRNA), named mammary gland proliferation-associated lncRNA (), in these processes. Transcriptomic analysis of mammary tissues from Met-deficient mice, supplemented either with a Met-Met/Met mixture or with Met alone, revealed significantly higher expression in the Met group compared to the mixture group, a finding recapitulated in a mammary epithelial cell model. Our findings suggested that hindered mammogenesis and milk protein synthesis by binding to eukaryotic initiation factor 4B (eIF4B). This interaction promoted the dephosphorylation of eIF4B at serine-422 by enhancing its association with protein phosphatase 2A (PP2A). Our study sheds light on the regulatory mechanisms of lncRNA-mediated dipeptide effects on mammary cell proliferation and milk protein synthesis. These insights underscore the potential benefits of utilizing dipeptides to improve milk protein in animals and potentially in humans.
先前的研究表明，在缺乏 l-蛋氨酸（Met）的孕鼠中，l-蛋氨酰-l-蛋氨酸（Met-Met）与 Met 的混合物比单独使用 Met 更能有效地促进乳腺发生和泌乳。本研究旨在探讨一种名为乳腺增殖相关长非编码 RNA（）的新型长非编码 RNA（lncRNA）在这些过程中的作用。对补充 Met-Met/Met 混合物或单独补充 Met 的 Met 缺乏型小鼠乳腺组织的转录组分析显示，与混合物组相比，Met 组中的表达显著升高，这一发现在乳腺上皮细胞模型中得到了重现。我们的研究结果表明，通过与真核起始因子 4B（eIF4B）结合， 抑制乳腺发生和乳蛋白合成。这种相互作用通过增强与蛋白磷酸酶 2A（PP2A）的结合，促进 eIF4B 在丝氨酸 422 上的去磷酸化。本研究揭示了 lncRNA 介导的二肽对乳腺细胞增殖和乳蛋白合成的调控机制。这些发现强调了利用二肽来提高动物（可能包括人类）乳蛋白的潜在益处。
