【原】纳尼？蜂粮中特异miRNA能够靶向蜜粉体内蛋白

导读：

最近几年以来，南京大学张辰宇教授有关小RNA研究的文章，有较大争议，主要在于是否植物来源的小RNA能够进入动物体内。科学界一直不是很相信，其中一个主要因素是其结果能否被其他人重复。相关报道见bioart公众号详文 闯入动物王国的植物miRNA丨BioArt推荐 而另外还有一个问题是，有些反对转基因农作物的人声称张辰宇教授反对转基因。

       在最新的一篇研究论文中，张辰宇团队报道，他们在蜜蜂中再次证实了这种植物对动物的跨界调控——蜜蜂幼虫是发育成蜂王还是工蜂，其食物中的植物microRNA在发挥作用。这一研究结果发表在8月31日的PloS Genetics上。

Fig 1. Comparison of the levels of plant and animal miRNAs in royal jelly, honey, beebread and pollen.

同行评议：

1、肯定，正面评论：

   这项新发现受到了Science杂志、《纽约时报》等媒体的关注。在接受《纽约时报》采访时，加州大学圣迭戈分校的细胞和分子医学教授付向东称张辰宇等人“做了一个细致的工作”，非常有趣；耶鲁大学的医学和病理学教授菲利普·阿斯肯纳瑟（Philip Askenase）则称“这是个大事”。 

    南方科技大学讲座教授、食品营养与安全研究所所长郭红卫就此评论道：“这是非常有意思的工作，通过采集和比较蜜蜂食物中的miRNA，发现蜂粮中特异miRNA能够靶向蜜蜂体内发育调控蛋白，影响蜂群三型分化。从植物源特异miRNA的发现到分子机制的解释，都表明了种间miRNA传递的重大生物学意义。”

    “食物能够影响摄食者的生长发育并不稀奇，但是以miRNA形式来调控摄食者发育，令人好奇和兴奋！那么摄食者和食物的固定关系是否为自然选择的结果，这些miRNA是否会存在物种间的流动，能否影响到人本身的发育，这些都是值得去思考和探索的问题，回答这些问题对未来可能在人类饮食方式，疾病诊断和治疗方面产生革命性的影响”，郭红卫表示。

2. 误解”和“偏见”

8月30日晚，《知识分子》科学新闻实验室特邀编辑黄永明与张辰宇教授进行长谈。张辰宇详细介绍了他的最新发现，他所遭遇的“误解”和“偏见”，并首次正面回应其发现对于转基因食品安全性究竟意味着什么，由于版权问题，本小编挑几段精彩对话，以飨读者！详见张辰宇：我不喜欢孟山都，但说我反对转基因是完全失实的。

延伸：张辰宇接受央视采访（wifi下，请点击播放！）

原文摘要：

Plant microRNAs in larval food regulate honeybee caste development

Abstract：The major environmental determinants of honeybee caste development come from larval nutrients: royal jelly stimulates the differentiation of larvae into queens, whereas beebread leads to worker bee fate. However, these determinants are not fully characterized. Here we report that plant RNAs, particularly miRNAs, which are more enriched in beebread than in royal jelly, delay development and decrease body and ovary size in honeybees, thereby preventing larval differentiation into queens and inducing development into worker bees. Mechanistic studies reveal that amTOR, a stimulatory gene in caste differentiation, is the direct target of miR162a. Interestingly, the same effect also exists in non-social Drosophila. When such plant RNAs and miRNAs are fed to Drosophila larvae, they cause extended developmental times and reductions in body weight and length, ovary size and fecundity. This study identifies an uncharacterized function of plant miRNAs that fine-tunes honeybee caste development, offering hints for understanding cross-kingdom interaction and co-evolution.

张辰宇教授

张辰宇，39岁,博士,南京大学教授,长江特聘教授, 博士生导师,南大生科院院长. 91-95年 日本德岛大学医学部 博士 95-99年 美国哈佛大学医学院 博士后 99-04年 美国哈佛大学医学院 研究助理教授(分子糖尿病学) 01-03年 南京大学生命科学学院 部分时教授, 03-现在 南京大学生命科学学院 全时教授,院长, 93年度 日本学术振兴会特别研究员奖 02年度 美国糖尿病学会青年学者奖. 03年度 中国国家自然科学基金委杰出青年基金. 主要从事身体的能量代谢及细胞的能量代谢的分子作用机理及与之相关的疾病,如肥胖,糖尿病的发病机理方面的研究.在研究中发现了UCP2 及O2--UCP2途径导致2型糖尿病的新的发病机理.其间,也曾系统性地研究了PGC-1a的功能.还发现了BAD与GK在线粒体上形成复合物,第一次把细胞凋亡与细胞的糖代谢联系在一起.论文在Cell, Nature, Science, JCI, Mol.Cell, PNAS,等杂志上发表40余篇.发表文章的总引用次数达2500次.张辰宇教授在糖尿病的基础研究方面有很好的研究基础.在本项目中主要协调各课题组涉及到的糖尿病的基础研究,包括分子生物学、细胞生物学和模式生物研究等.  

代表性文章:

    1. Krauss S, Zhang CY, Lowell BB. The Mitochondrial Uncoupling Protein Homologues. Nature Reviews Molecular Cell Biology, 6(3):248-61, 2005.

    2. Balthasar N, Dalgaard LT, Lee CE, Yu J, Funahashi H, Williams T, Ferreira M, Tang V, McGovern RA, Kenny CD, Christiansen LM, Edelstein E, Choi B, Boss O, Aschkenasi C, Zhang CY, Mountjoy K, Kishi T, Elmquist JK, Lowell BB. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell, 123(3):493-505,2005.

    3. Zhang CY, Parton LE, Ye CP, Krauss S, Shen R, Lin CT, Porco JA Jr, Lowell BB. Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets. Cell Metabolism, 3(6):417-27, 2006.

    4. Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang CY, Xu C, Vianna CR, Balthasar N, Lee CE, Elmquist JK, Cowley MA, Lowell BB.Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature, 449(7159):228-32, 2007.

    5. Danial NN, Walensky LD, Zhang CY, Choi CS, Fisher JK, Molina AJ, Datta SR, Pitter KL, Bird GH, Wikstrom JD, Deeney JT, Robertson K, Morash J, Kulkarni A, Neschen S, Kim S, Greenberg ME, Corkey BE, Shirihai OS, Shulman GI, Lowell BB, Korsmeyer SJ.Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nature Medicine, 14(2):144-53, 2008.

    回国后发表的文章:

    *1. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY.Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008 Oct;18(10):997-1006.

    *2. Zhang Y, Liu D, Chen X, Li J, Li L, Bian Z, Sun F, Lu J, Yin Y, Cai X, Sun Q, Wang K, Ba Y, Wang Q, Wang D, Yang J, Liu P, Xu T, Yan Q, Zhang J, Zen K, Zhang CY. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell. 2010 Jul 9;39(1):133-44.

    *3. Zhang L, Hou D, Chen X, Li D, Zhu L, Zhang Y, Li J, Bian Z, Liang X, Cai X, Yin Y, Wang C, Zhang T, Zhu D, Zhang D, Xu J, Chen Q, Ba Y, Liu J, Wang Q, Chen J, Wang J, Wang M, Zhang Q, Zhang J, Zen K, Zhang CY. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res. 2012 Jan;22(1):107-26.

    *4. Chen X, Gao C, Li H, Huang L, Sun Q, Dong Y, Tian C, Gao S, Dong H, Guan D, Hu X, Zhao S, Li L, Zhu L, Yan Q, Zhang J, Zen K, Zhang CY. Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products. Cell Res. 2010 Oct;20(10):1128-37.

    *5. Wang C, Yang C, Chen X, Yao B, Yang C, Zhu C, Li L, Wang J, Li X, Shao Y, Liu Y, Ji J, Zhang J, Zen K, Zhang CY, Zhang C. Altered profile of seminal plasma microRNAs in the molecular diagnosis of male infertility. Clin Chem. 2011 Dec;57(12):1722-31.

    *6. Hu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y, Chen Y, Xu L, Zen K, Zhang CY, Shen H. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol. 2010 Apr 1;28(10):1721-6.

    *7. Li LM, Hu Z, Zhou ZX, Chen X, Liu FY, Zhang JF, Shen HB, Zhang CY, Zen K. Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma. Cancer Res. 2010 Dec 1;70(23):9798-807.

    *8. Zen K, Zhang CY. Circulating MicroRNAs: a novel class of biomarkers to diagnose and monitor human cancers. Med Res Rev. Epub 2010 Nov 9.

    *9. Chen X, Liang H, Zhang J, Zen K, Zhang CY. Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol. Trends Cell Biol. Epub 2012 Jan 17.

    *10. Chen X, Guo X, Zhang H, Xiang Y, Chen J, Yin Y, Cai X, Wang K, Wang G, Ba Y, Zhu L, Wang J, Yang R, Zhang Y, Ren Z, Zen K, Zhang J, Zhang CY. Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene. 2009 Mar 12;28(10):1385-92.

    11. Chen X, Liang H, Zhang J, Zen K, Zhang CY. Horizontal transfer of microRNAs: molecular mechanisms and clinical applications.Protein Cell. 2012 Jan;3(1):28-37.

    12. Liu R, Chen X, Du Y, Yao W, Shen L, Wang C, Hu Z, Zhuang R, Ning G, Zhang C, Yuan Y, Li Z, Zen K, Ba Y, Zhang CY. Serum MicroRNA Expression Profile as a Biomarker in the Diagnosis and Prognosis of Pancreatic Cancer. Clin Chem. Clin Chem. Epub 2011 Dec 22.

    13. Chen X, Hu Z, Wang W, Ba Y, Ma L, Zhang C, Wang C, Ren Z, Zhao Y, Wu S, Zhuang R, Zhang Y, Hu H, Liu C, Xu L, Wang J, Shen H, Zhang J, Zen K, Zhang CY. Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis.Int J Cancer. 2012 Apr 1;130(7):1620-8.

    14. Wang K, Li P, Dong Y, Cai X, Hou D, Guo J, Yin Y, Zhang Y, Li J, Liang H, Yu B, Chen J, Zen K, Zhang J, Zhang CY, Chen X. A microarray-based approach identifies ADP ribosylation factor-like protein 2 as a target of microRNA-16. J Biol Chem. J Biol Chem. 2011 Mar 18;286(11):9468-76.

    15. Liu R, Zhang C, Hu Z, Li G, Wang C, Yang C, Huang D, Chen X, Zhang H, Zhuang R, Deng T, Liu H, Yin J, Wang S, Zen K, Ba Y, Zhang CY. A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis.Eur J Cancer. 2011 Mar;47(5):784-91.

    16. Xie L, Wang T, Yu S, Chen X, Wang L, Qian X, Yu L, Ding Y,Zhang CY, Liu B. Cell-free miR-24 and miR-30d, potential diagnostic biomarkers in malignant effusions.Clin Biochem. 2011 Feb;44(2-3):216-20.

    17. Zhang C, Wang C, Chen X, Yang C, Li K, Wang J, Dai J, Hu Z, Zhou X, Chen L, Zhang Y, Li Y, Qiu H, Xing J, Liang Z, Ren B, Yang C, Zen K, Zhang CY. Expression profile of microRNAs in serum: a fingerprint for esophageal squamous cell carcinoma. Clin Chem. 2010 Dec;56(12):1871-9.

    18. Xie L, Chen X, Wang L, Qian X, Wang T, Wei J, Yu L, Ding Y, Zhang CY, Liu B. Cell-free miRNAs may indicate diagnosis and docetaxel sensitivity of tumor cells in malignant effusions. BMC Cancer. 2010 Oct 28;10:591.

    19. Guo J, Dong Q, Fang Z, Chen X, Lu H, Wang K, Yin Y, Cai X, Zhao N, Chen J, Zen K, Zhang J, Zhang CY. Identification of miRNAs that are associated with tumor metastasis in neuroblastoma. Cancer Biol Ther. 2010 Mar;9(6): 446-52.

    20. Chen X, Li Q, Wang J, Guo X, Jiang X, Ren Z, Weng C, Sun G, Wang X, Liu Y, Ma L, Chen JY, Wang J, Zen K, Zhang J,Zhang CY. Identification and characterization of novel amphioxus microRNAs by Solexa sequencing. Genome Biol. 2009;10(7):R78.

    21. Li S, Chen X, Zhang H, Liang X, Xiang Y, Yu C, Zen K, Li Y, Zhang CY. Differential expression of microRNAs in mouse liver under aberrant energy metabolic status. J Lipid Res. 2009 Sep;50(9):1756-65.

    22. Chen X, Wang K, Chen J, Guo J, Yin Y, Cai X, Guo X, Wang G, Yang R, Zhu L, Zhang Y, Wang J, Xiang Y, Weng C, Zen K, Zhang J, Zhang CY. In vitro evidence suggests that miR-133a-mediated regulation of uncoupling protein 2 (UCP2) is an indispensable step in myogenic differentiation. J Biol Chem. 2009 Feb 20;284(8):5362-9.

    23. Zhang H, Li J, Liang X, Luo Y, Zen K, Zhang CY. Uncoupling Protein 2 Negatively Regulates Glucose-Induced Glucagon-Like Peptide-1 (GLP-1) Secretion. J Mol Endocrinol. 2012 Jan 18.

    24. Xu W, Guo T, Zhang Y, Jiang X, Zhang Y, Zen K, Yu B, Zhang CY. The inhibitory effect of dexamethasone on platelet-derived growth factor-induced vascular smooth muscle cell migration through up-regulating PGC-1α expression. Exp Cell Res. 2011 May 1;317(8):1083-92.

    25. Gu Z, Li J, Gao S, Gong M, Wang J, Xu H, Zhang CY, Wang J. InterMitoBase: an annotated database and analysis platform of protein-protein interactions for human mitochondria. BMC Genomics. 2011 Jun 30;12:335.

    26. Gong M, Li J, Wang M, Wang J, Zen K, Zhang CY. The evolutionary trajectory of mitochondrial carrier family during metazoan evolution. BMC Evol Biol. 2010 Sep 16;10:282.

    27. Xu W, Hou D, Jiang X, Lu Z, Guo T, Liu Y, Wang D, Zen K, Yu B, Zhang CY. The protective role of peroxisome proliferator-activated receptor γ coactivator-1α in hyperthyroid cardiac hypertrophy.J Cell Physiol. 2011 Nov 21. doi: 10.1002/jcp.24015.

    28. Zhang D, Shen M, Mikita A, Zhang W, Liu Y, Liu Q, Dai Y,Zhang CY, Zheng S, Zheng XX. Targeting Uncoupling Protein-2 Improves Islet Graft Function. Cell Transplant.2011;20(3):421-9.

    29. Sun LB, Zhang Y, Wang Q, Zhang H, Xu W, Zhang J, Xiang J, Li QG, Xiang Y, Wang DJ, Zhang CY. Serum palmitic acid-oleic acid ratio and the risk of coronary artery disease: a case-control study. J Nutr Biochem. 2011 Apr;22(4):311-7.

    30. Chen K, Sun G, Lv Z, Wang C, Jiang X, Li D, Zhang CY. Molecular cloning of amphioxus uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system. Biochem Biophys Res Commun. 2010 Oct 1;400(4):701-6.

    31. Yang J, Li JH, Wang J,Zhang CY. Molecular modeling of BAD complex resided in a mitochondrion integrating glycolysis and apoptosis. J Theor Biol. 2010 Sep 21;266(2):231-41.

    32. Zhu L, Wang Q, Zhang L, Fang Z, Zhao F, Lv Z, Gu Z, Zhang J, Wang J, Zen K, Xiang Y, Wang D, Zhang CY. Hypoxia induces PGC-1α expression and mitochondrial biogenesis in the myocardium of TOF patients. Cell Res. 2010 Jun;20(6):676-87.

    33. Jiang X, Zhang Y, Hou D, Zhu L, Xu W, Ding L, Qi X, Sun G, Liu C, Zhang J, Zen K, Xiang Y, Zhang CY. 17beta-estradiol inhibits oleic acid-induced rat VSMC proliferation and migration by restoring PGC-1alpha expression. Mol Cell Endocrinol. 2010 Feb 5;315(1-2):74-80.

    34. Wang C, Sun G, Chen K, Lv Z, Peng S, Jiang X, Xiang Y,Zhang CY. Molecular cloning of lamprey uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system. Mitochondrion. 2010 Jan;10(1):54-61.

    35. Zhu L, Sun G, Zhang H, Zhang Y, Chen X, Jiang X, Jiang X, Krauss S, Zhang J, Xiang Y, Zhang CY. PGC-1alpha is a key regulator of glucose-induced proliferation and migration in vascular smooth muscle cells. PLoS One. 2009;4(1):e4182.

    36. Qu A, Jiang C, Xu M, Zhang Y, Zhu Y, Xu Q, Zhang CY, Wang X. PGC-1alpha attenuates neointimal formation via inhibition of vascular smooth muscle cell migration in the injured rat carotid artery. Am J Physiol Cell Physiol. 2009 Sep;297(3):C645-53.

    37. Luo Y, Zhu W, Jia J, Zhang CY, Xu Y. NMDA receptor dependent PGC-1alpha up-regulation protects the cortical neuron against oxygen-glucose deprivation/reperfusion injury. J Mol Neurosci. 2009 Sep;39(1-2):262-8.

    38. Jin X, Yang YD, Chen K, Lv ZY, Zheng L, Liu YP, Chen SH, Yu CH, Jiang XY, Zhang CY, Li YM. HDMCP uncouples yeast mitochondrial respiration and alleviates steatosis in L02 and hepG2 cells by decreasing ATP and H2O2 levels: a novel mechanism for NAFLD. J Hepatol. 2009 May;50(5):1019-28.

    39. Zhang Y, Liu C, Zhu L, Jiang X, Chen X, Qi X, Liang X, Jin S, Zhang P, Li Q, Wang D, Liu X, Zeng K, Zhang J, Xiang Y, Zhang CY. PGC-1alpha inhibits oleic acid induced proliferation and migration of rat vascular smooth muscle cells. PLoS One. 2007 Nov 7;2(11):e1137.

    40. Zhang Y, Ba Y, Liu C, Sun G, Ding L, Gao S, Hao J, Yu Z, Zhang J, Zen K, Tong Z, Xiang Y, Zhang CY. PGC-1alpha induces apoptosis in human epithelial ovarian cancer cells through a PPARgamma-dependent pathway. Cell Res. 2007 Apr;17(4):363-73.