The miR-15/107 group of microRNA genes: evolutionary biology, cellular functions, and roles in human diseases.
The miR-15/107 group of microRNA genes: evolutionary biology, cellular functions, and roles in human diseases.
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DOI：
10.1016/j.jmb.2010.07.051
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发表时间：
2010-09-24
影响因子：
5.6
通讯作者：
Nelson PT
中科院分区：
文献类型：
--
作者：
Finnerty JR;Wang WX;Hébert SS;Wilfred BR;Mao G;Nelson PT
MiR-15/107组microRNA(MiRNA)基因越来越受到重视，在人类中发挥关键功能。这些miRNAs调控参与脊椎动物细胞分裂、新陈代谢、应激反应和血管生成的基因表达。MiR-15/107组还与人类癌症、心血管疾病和包括阿尔茨海默病在内的神经退行性疾病有关。本文综述了(1)miR-15/107组成员基因的进化，(2)miRNAs在哺乳动物组织中的表达水平，(3)不同miRNAs重叠基因调控功能的证据，(4)由miR-15/107组miRNAs调控的正常生化途径，以及(5)这些miRNAs在人类疾病中所起的作用。该组中的成员是根据成熟miRNAs‘5’端附近的序列相似性定义的：所有都包括序列AGCAGC。这组miRNAs的系统发育是不完整的，因此目前不可能对其进行明确的分类(例如，指定为“超家族”)。到目前为止，所有研究的脊椎动物都表达miR-15a、-15b、-16、-103和-107，而只有哺乳动物表达miR-195、-424、-497、-503和-646。MiR-15/107组多个不同的miRNAs在人体组织中高水平表达。我们使用新的miRNA图谱芯片提供了所有已知miR-15/107组成员在人脑皮质灰质和白质中表达的数据。MiR-15/107组成员靶向的mRNAs有广泛重叠。我们展示了来自培养的H4癌细胞的新数据，这些数据证明了miR-16和miR-103靶向的mRNAs相似之处，也支持了成熟的miRNAs‘5’种子区域在mRNA靶标识别中的重要性。总之，miR-15/107组miRNA基因对于进化生物学家、miRNA生物化学家和面向临床的翻译研究人员来说都是一个迷人的研究主题。
The miR-15/107 group of microRNA (miRNA) genes is increasingly appreciated to serve key functions in humans. These miRNAs regulate gene expression involved in cell division, metabolism, stress response, and angiogenesis in vertebrate species. The miR-15/107 group has also been implicated in human cancers, cardiovascular disease, and neurodegenerative diseases including Alzheimer’s disease. Here, we provide an overview of (1) the evolution of miR-15/107 group member genes, (2) the expression levels of the miRNAs in mammalian tissues, (3) evidence for overlapping gene regulatory functions by the different miRNAs, (4) the normal biochemical pathways regulated by miR-15/107 group miRNAs, and (5) the roles played by these miRNAs in human diseases. Membership in this group is defined on the basis of sequence similarity near the mature miRNAs’ 5′ end: all include the sequence AGCAGC. Phylogeny of this group of miRNAs is incomplete so a definitive taxonomic classification (for example, designation as a “superfamily”) is currently not possible. While all vertebrates studied to date express miR-15a, -15b, -16, -103, and -107, mammals alone are known to express miR-195, -424, -497, -503, and -646. Multiple different miRNAs in the miR-15/107 group are expressed at moderate-to-high levels in human tissues. We present data on the expression of all known miR-15/107 group members in human cerebral cortical gray and white matter using new miRNA profiling microarrays. There is extensive overlap in the mRNAs targeted by miR-15/107 group members. We show new data from cultured H4 cancer cells that demonstrate similarities in mRNAs targeted by miR-16 and miR-103, and also support the importance of the mature miRNAs’ 5′ seed region in mRNA target recognition. In conclusion, the miR-15/107 group of miRNA genes is a fascinating topic of study for evolutionary biologists, miRNA biochemists, and clinically-oriented translational researchers alike.
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通讯作者：
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