生物谷报道:在6月29日著名国际杂志Cell上发表的一篇文章中,发布了一张microRNA表达图谱,该结果显示,哺乳动物为数众多的microRNA只是起源于少数几个microRNA基因,而且组织或细胞特异的microRNA很少。
该图谱对来自人类和啮齿类的26种正常、肿瘤组织的细胞的microRNA表达进行了定量测定。“他们掌握了一种极为有用的资源,”Dartmouth医学院Victor Ambros说(未参与实验),他们在研究中收集的组织种类非常多,并对这些组织中的microRNA的特征进行了系统性分析。 新绘制的microRNA表达图谱含有许多关于microRNA结构、序列、表达方式和进化的有用信息。Ambros认为这是一个基本数据库,为研究发育和疾病有关的microRNA世界提供了重要线索。
microRNA是动物、植物和病毒中普遍存在的非编码小RNA,通过干扰mRNA的功能调节基因表达。科研人员已经鉴定出多种哺乳动物microRNA,但对这些microRNA中大多数的表达水平和特征都是未知的。
洛克菲勒大学Pablo Landgraf率领的研究小组克隆并测序了256个哺乳动物小RNA数据库中的30多万个序列,找到了大约400个在任何组织都表达的microRNA——比之前预期的要少。约翰霍普金斯大学Joshua Mendell说,这个结果提示在其它研究中找到的几个百microRNA是未知的。
Landgraf等还发现他们测序的microRNA克隆中,97%的来自不到300个microRNA。文章共同作者、瑞士Basel大学Mihaela Zavolan认为许多microRNA在各种组织间是低背景水平表达的(low background level),现在不能确定这些“痕量”microRNA的功能,但很有可能大多数microRNA的功能是不相关的。他们还发现这些稀少的microRNA在物种间的保守性很差。
研究人员发现组织或者细胞特异的microRNA种类很少,相反,细胞系和组织之间的差异经常局限在一小部分普遍存在的microRNA的表达水平的变化。Mendell说缺乏细胞、组织特异的microRNA并不意味着microRNA没有区分肿瘤起源、组织或细胞的作用。真正重要的是一个给定样本表达的所有microRNA。
此次研究只鉴别出33种新的哺乳动物microRNA。“这真是一件重量级研究,”Ambros说,意味着我们渐渐补全了哺乳动物microRNA的目录,至少是丰富了主要器官和组织的microRNA,还有可能某些功能重要的microRNA只在个别种类细胞中表达,所以没有被检测到。
Table 1. miRNAs Identified in This Study and Not Listed in miRBase (Release 9.1)
Table 1. miRNAs Identified in This Study and Not Listed in miRBase (Release 9.1)
Human miRNA Sequence Clone # Mouse miRNA
Sequence Clone # Rat miRNA Sequence Clone #
miR-872__FM AAGGUUACUUGUUAGUUCAGG 11 miR-872 AAGGUUACUUGUUAGUUCAGG 394 miR-872 AAGGUUACUUGUUAGUUCAGG 373
miR-879 AGAGGCUUAUAGCUCUAAGCC 33 miR-879 AGAGGCUUAUAGCUCUAAGCC 5
miR-8822 AGGAGAGAGUUAGCGCAUUAGU 1 miR-882a6 AUGGGAAUGUUAGAGCAUUAGC 0
miR-882b AUGGCAAUGUUAGAGCAUUAGC 0
miR-874 CUGCCCUGGCCCGAGGGACCGA 17 miR-874 CUGCCCUGGCCCGAGGGACCGA 2 miR-874 CUGCCCUGGCCCGAGGGACCGA 0
miR-877 GUAGAGGAGAUGGCGCAGGG 40 miR-877 GUAGAGGAGAUGGCGCAGGG 6 miR-877 GUAGAGGAGAUGGCGCAGGG 2
miR-297c3 AUGUAUGUGUGCAUGUACAUGU 16
| miR-743b4 GAAAGACAUCAUGCUGAAUAGA 8 | miR-743b7 GAAAGACACCAUACUGAAUAGA 0
| miR-883a UAACUGCAACAGCUCUCAGUAU 6
| miR-883b UAACUGCAACAUCUCUCAGUAU 1 | miR-883 UAACUGCAACAUCUCUCAGUAU 0
| miR-880 UACUCCAUCCUCUCUGAGUAGA 119 | miR-880 UACUCCAUUCAUUCUGAGUAGA 3
| miR-878 GCAUGACACCACACUGGGUAGA 22 | miR-878 GCAUGACACCAUACUGGGUAGA 1
| miR-874 AACUGUGUCUUUUCUGAAUAGA 60 | miR-881 AACUGUGGCAUUUCUGAAUAGA 0
miR-871__FM UAUUCAGAUUAGUGCCAGUCAUG 2 | miR-871 UAUUCAGAUUAGUGCCAGUCAUG 11 | miR-871 UAUUCAGAUUGGUGCCGGUCACA 0
| miR-8901 UACUUGGAAAGGCAUCAGUUG 10
| miR-888 UACUCAAAAAGCUGUCAGUCA 16
| miR-465d UAUUUAGAAUGGUACUGAUGUG 0
| miR-892b CACUGGCUCCUUUCUGGGUAGA 14 | miR-465c UAUUUAGAAUGGCGCUGAUCUG 42
| miR-891b UGCAACUUACCUGAGUCAUUGA 4
| miR-891a UGCAACGAACCUGAGCCACUGA 24
| miR-466f5 UACGUGUGUGUGCAUGUGCAUG 7
| miR-466e GAUGUGUGUGUACAUGUACAUA 1.5
| miR-466b GAUGUGUGUGUACAUGUACAUG 7
| miR-466b8 UAUGUGUGUGUGUAUGUCCAUG 1
| miR-466c GAUGUGUGUGUGCAUGUACAUA 11
| miR-466c UGUGAUGUGUGCAUGUACAUG 2
| miR-467e AUAAGUGUGAGCAUGUAUAUGU 125
| miR-466d UGUGUGUGCGUACAUGUACAUG 4
| miR-466g AUACAGACACAUGCACACACA 2
| miR-466h UGUGUGCAUGUGCUUGUGUGUA 4
miR-885 UCCAUUACACUACCCUGCCUCU 5
miR-887 GUGAACGGGCGCCAUCCCGAGG 3
miR-886 CGCGGGUGCUUACUGACCCUU 16
The predominantly cloned sequence and orthologs are indicated. Bars beside the name indicate clustered miRNAs.
[1] Part of the cluster-hsa-mir-888(6), epididymis-specific expression.
[2] Part of the cluster-mmu-mir-134(33), enriched in embryonic tissue.
[3] Part of the cluster-mmu-mir-297a-1(46).
[4] Part of the cluster-mmu-mir-463(19), epididymis (testis) enriched expression.
[5] Part of the cluster-mmu-mir-297a-3(43).
[6] Part of the cluster-rno-mir-134(41).
[7] Part of the cluster-rno-mir-463(12).
[8] Part of the cluster-rno-mir-297c(4); Abbreviations are as follows: FM: “from mouse”; the same miRNA sequence as in mouse was cloned but could not be found in the current human assembly.
原始出处:
Cell, Vol 129, 1401-1414, 29 June 2007