两个 miRNA 簇，miR-34b/c 和 miR-449，对于正常的大脑发育、运动纤毛发生和精子发生是必不可少的。
Two miRNA clusters, miR-34b/c and miR-449, are essential for normal brain development, motile ciliogenesis, and spermatogenesis.
机构信息
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557;Department of Histology and Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China; and.
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557;
出版信息
Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):E2851-7. doi: 10.1073/pnas.1407777111. Epub 2014 Jun 30.
Abstract
Ablation of a single miRNA gene rarely leads to a discernable developmental phenotype in mice, in some cases because of compensatory effects by other functionally related miRNAs. Here, we report that simultaneous inactivation of two functionally related miRNA clusters (miR-34b/c and miR-449) encoding five miRNAs (miR-34b, miR-34c, miR-449a, miR-449b, and miR-449c) led to sexually dimorphic, partial perinatal lethality, growth retardation, and infertility. These developmental defects correlated with the dysregulation of ∼ 240 target genes, which are mainly involved in three major cellular functions, including cell-fate control, brain development and microtubule dynamics. Our data demonstrate an essential role of a miRNA family in brain development, motile ciliogenesis, and spermatogenesis.
摘要
在小鼠中，单个 miRNA 基因的缺失很少导致明显的发育表型，在某些情况下是因为其他功能相关的 miRNA 产生了补偿作用。在这里，我们报告说，两个功能相关的 miRNA 簇（miR-34b/c 和 miR-449）的同时失活，编码五个 miRNA（miR-34b、miR-34c、miR-449a、miR-449b 和 miR-449c）导致了性别二态性、部分围产期致死、生长迟缓和不育。这些发育缺陷与约 240 个靶基因的失调相关，这些靶基因主要涉及三个主要的细胞功能，包括细胞命运控制、大脑发育和微管动力学。我们的数据表明 miRNA 家族在大脑发育、运动纤毛发生和精子发生中具有重要作用。
相似文献
1
Two miRNA clusters, miR-34b/c and miR-449, are essential for normal brain development, motile ciliogenesis, and spermatogenesis.两个 miRNA 簇，miR-34b/c 和 miR-449，对于正常的大脑发育、运动纤毛发生和精子发生是必不可少的。
Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):E2851-7. doi: 10.1073/pnas.1407777111. Epub 2014 Jun 30.
2
Motile cilia of the male reproductive system require miR-34/miR-449 for development and function to generate luminal turbulence.雄性生殖系统的游动纤毛需要 miR-34/miR-449 来发育和发挥功能，以产生管腔涡流。
Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3584-3593. doi: 10.1073/pnas.1817018116. Epub 2019 Jan 18.
3
Oligoasthenoteratozoospermia and infertility in mice deficient for miR-34b/c and miR-449 loci.miR-34b/c和miR-449基因座缺失小鼠的少弱畸精子症与不育症
PLoS Genet. 2014 Oct 16;10(10):e1004597. doi: 10.1371/journal.pgen.1004597. eCollection 2014 Oct.
4
mir-34b/c and mir-449a/b/c are required for spermatogenesis, but not for the first cleavage division in mice.miR-34b/c 和 miR-449a/b/c 对于精子发生是必需的，但对于小鼠的第一次卵裂分裂则不是必需的。
Biol Open. 2015 Jan 23;4(2):212-23. doi: 10.1242/bio.201410959.
5
MicroRNA-449 and microRNA-34b/c function redundantly in murine testes by targeting E2F transcription factor-retinoblastoma protein (E2F-pRb) pathway.miRNA-449 和 miRNA-34b/c 通过靶向 E2F 转录因子-视网膜母细胞瘤蛋白（E2F-pRb）通路在小鼠睾丸中发挥冗余功能。
J Biol Chem. 2012 Jun 22;287(26):21686-98. doi: 10.1074/jbc.M111.328054. Epub 2012 May 8.
6
MicroRNA expression profiles in human testicular tissues of infertile men with different histopathologic patterns.不同组织病理学类型不育症患者睾丸组织中 microRNA 表达谱。
Fertil Steril. 2014 Jan;101(1):78-86.e2. doi: 10.1016/j.fertnstert.2013.09.009. Epub 2013 Oct 17.
7
MicroRNA signature in various cell types of mouse spermatogenesis: evidence for stage-specifically expressed miRNA-221, -203 and -34b-5p mediated spermatogenesis regulation.小鼠精子发生过程中各种细胞类型的 microRNA 特征：证据表明 miRNA-221、-203 和 -34b-5p 的表达具有阶段特异性，可调节精子发生。
Biol Cell. 2012 Nov;104(11):677-92. doi: 10.1111/boc.201200014. Epub 2012 Sep 24.
8
[Expression and significance of microRNAs in the p53 pathway in ovarian cancer cells and serous ovarian cancer tissues].[微小RNA在卵巢癌细胞及浆液性卵巢癌组织p53信号通路中的表达及意义]
Zhonghua Zhong Liu Za Zhi. 2011 Dec;33(12):885-90.
9
Dramatic changes in 67 miRNAs during initiation of first wave of spermatogenesis in Mus musculus testis: global regulatory insights generated by miRNA-mRNA network analysis.小家鼠睾丸中第一波精子发生起始过程中67种微小RNA的显著变化：通过微小RNA-信使核糖核酸网络分析获得的全局调控见解
Biol Reprod. 2014 Sep;91(3):69. doi: 10.1095/biolreprod.114.119305. Epub 2014 Aug 13.
10
miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110.miR-34/449 微 RNA 通过抑制 cp110 来促进游动纤毛的发生。
Nature. 2014 Jun 5;510(7503):115-20. doi: 10.1038/nature13413.
引用本文的文献
1
Global knowledge mapping and emerging research trends in non-coding RNAs related to animal and plant male sterility: A visual analysis of CiteSpace maps.与动植物雄性不育相关的非编码RNA的全球知识图谱及新兴研究趋势：CiteSpace图谱的可视化分析
Medicine (Baltimore). 2025 Jun 6;104(23):e42612. doi: 10.1097/MD.0000000000042612.
2
Oxidative-Stress-Mediated Epigenetic Dysregulation in Spermatogenesis: Implications for Male Infertility and Offspring Health.氧化应激介导的精子发生过程中的表观遗传失调：对男性不育和后代健康的影响。
Genes (Basel). 2025 Jan 17;16(1):93. doi: 10.3390/genes16010093.
3
Region-specific roles of oviductal motile cilia in oocyte/embryo transport and fertility†.输卵管活动纤毛在卵母细胞/胚胎运输及生育力中的区域特异性作用†
Biol Reprod. 2025 Apr 13;112(4):651-662. doi: 10.1093/biolre/ioaf005.
4
Exposure to childhood maltreatment is associated with specific epigenetic patterns in sperm.童年期受虐待与精子中的特定表观遗传模式有关。
Mol Psychiatry. 2025 Jun;30(6):2635-2644. doi: 10.1038/s41380-024-02872-3. Epub 2025 Jan 3.
5
Novel insights into non-coding RNAs and their role in hydrocephalus.非编码RNA及其在脑积水发病机制中的作用的新见解。
Neural Regen Res. 2026 Feb 1;21(2):636-647. doi: 10.4103/NRR.NRR-D-24-00963. Epub 2024 Dec 16.
6
Motile Cilia in Female and Male Reproductive Tracts and Fertility.女性和男性生殖道中的运动性纤毛与生育能力
Cells. 2024 Nov 28;13(23):1974. doi: 10.3390/cells13231974.
7
miR-449, identified through antiandrogen exposure, mitigates functional biomarkers associated with ovarian cancer risk.通过抗雄激素暴露鉴定出的miR-449可减轻与卵巢癌风险相关的功能生物标志物。
Sci Rep. 2024 Dec 2;14(1):29937. doi: 10.1038/s41598-024-80173-z.
8
Harnessing the power of miRNAs for precision diagnosis and treatment of male infertility.利用微小RNA的力量实现男性不育症的精准诊断与治疗。
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):3271-3296. doi: 10.1007/s00210-024-03594-7. Epub 2024 Nov 13.
9
Exploring Differentially Expressed Sperm miRNAs in Idiopathic Recurrent Pregnancy Loss and Their Association with Early Embryonic Development.探索特发性复发性流产中差异表达的精子微小RNA及其与早期胚胎发育的关系。
Noncoding RNA. 2024 Jul 21;10(4):41. doi: 10.3390/ncrna10040041.
10
In Vitro Culture of Mammalian Embryos: Is There Room for Improvement?哺乳动物胚胎的体外培养：是否有改进的空间？
Cells. 2024 Jun 7;13(12):996. doi: 10.3390/cells13120996.
本文引用的文献
1
miR-34b regulates multiciliogenesis during organ formation in zebrafish.miR-34b 在斑马鱼器官形成过程中调节多纤毛发生。
Development. 2013 Jul;140(13):2755-64. doi: 10.1242/dev.092825. Epub 2013 May 22.
2
Differential analysis of gene regulation at transcript resolution with RNA-seq.基于 RNA-seq 的转录分辨率下基因调控的差异分析。
Nat Biotechnol. 2013 Jan;31(1):46-53. doi: 10.1038/nbt.2450. Epub 2012 Dec 9.
3
MiRNA-29: a microRNA family with tumor-suppressing and immune-modulating properties.miRNA-29：具有抑瘤和免疫调节特性的 microRNA 家族。
Curr Mol Med. 2013 May;13(4):572-85. doi: 10.2174/1566524011313040009.
4
Intact p53-dependent responses in miR-34-deficient mice.miR-34 缺陷型小鼠中完整的 p53 依赖性反应。
PLoS Genet. 2012;8(7):e1002797. doi: 10.1371/journal.pgen.1002797. Epub 2012 Jul 26.
5
The RNase III enzyme DROSHA is essential for microRNA production and spermatogenesis.RNase III 酶 DROSHA 对于 microRNA 的产生和精子发生至关重要。
J Biol Chem. 2012 Jul 20;287(30):25173-90. doi: 10.1074/jbc.M112.362053. Epub 2012 Jun 4.
6
MicroRNA-449 and microRNA-34b/c function redundantly in murine testes by targeting E2F transcription factor-retinoblastoma protein (E2F-pRb) pathway.miRNA-449 和 miRNA-34b/c 通过靶向 E2F 转录因子-视网膜母细胞瘤蛋白（E2F-pRb）通路在小鼠睾丸中发挥冗余功能。
J Biol Chem. 2012 Jun 22;287(26):21686-98. doi: 10.1074/jbc.M111.328054. Epub 2012 May 8.
7
DNA methylation of tumor suppressor miRNA genes: a lesson from the miR-34 family.肿瘤抑制 miRNA 基因的 DNA 甲基化：miR-34 家族的教训。
Epigenomics. 2011 Feb;3(1):83-92. doi: 10.2217/epi.10.74.
8
miR-34 miRNAs provide a barrier for somatic cell reprogramming.miR-34 miRNAs 为体细胞重编程提供了一道屏障。
Nat Cell Biol. 2011 Oct 23;13(11):1353-60. doi: 10.1038/ncb2366.
9
MicroRNAs as post-transcriptional machines and their interplay with cellular networks.微小 RNA 作为转录后机器及其与细胞网络的相互作用。
Adv Exp Med Biol. 2011;722:59-74. doi: 10.1007/978-1-4614-0332-6_4.
10
Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs.弱的种子配对稳定性和高的靶标位点丰度降低了 lsy-6 和其他 microRNAs 的效率。
Nat Struct Mol Biol. 2011 Sep 11;18(10):1139-46. doi: 10.1038/nsmb.2115.
Zotero 插件