State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, China.
BMC Genomics. 2011 Dec 14;12:605. doi: 10.1186/1471-2164-12-605.
MicroRNAs (miRNAs) play important roles in regulating the expression of protein-coding genes by directing the degradation and/or repression of the translation of gene transcripts. Growing evidence shows that miRNAs are indispensable player in organismal development with its regulatory role in the growth and differentiation of cell lineages. However, the roles of miRNA-mediated regulation in environmental adaptation of organisms are largely unknown. To examine this potential regulatory capability, we characterized microRNAomes from the brain of zebrafish raised under normal (28 °C) and cold-acclimated (10 °C, 10 days) conditions using Solexa sequencing. We then examined the expression pattern of the protein-coding genes under these two conditions with Affymetrix Zebrafish Genome Array profiling. The potential roles of the microRNAome in the transcriptomic cold regulation in the zebrafish brain were investigated by various statistical analyses.
Among the total 214 unique, mature zebrafish miRNAs deposited on the miRBase website (release 16), 175 were recovered in this study. In addition, we identified 399 novel, mature miRNAs using multiple miRNA prediction methods. We defined a set of 25 miRNAs differentially expressed under the cold and normal conditions and predicted the molecular functions and biological processes that they involve through Gene Ontology (GO) annotation of their target genes. On the other hand, microarray analysis showed that genes related to mRNA processing and response to stress were overrepresented among the up-regulated genes in cold-stress, but are not directly corresponding to any of the GO molecular functions and biological processes predicted from the differential miRNAs. Using several statistical models including a novel, network-based approach, we found that miRNAs identified in this study, either individually or together, and either directly or indirectly (i.e., mediated by transcription factors), only make minor contribution to the change in gene expression patterns under the low-temperature condition.
Our results suggest that the cold-stress response of mRNA expression may be governed mainly through regulatory modes other than miRNA-mediated regulation. MiRNAs in animal brains might act more as developmental regulators than thermal adaptability regulators.
微小 RNA(miRNAs)通过指导基因转录物的降解和/或抑制翻译,在调节蛋白质编码基因的表达方面发挥重要作用。越来越多的证据表明,miRNAs 是生物体发育过程中不可或缺的参与者,其在细胞谱系的生长和分化中具有调节作用。然而,miRNA 介导的调节在生物体对环境的适应中的作用在很大程度上是未知的。为了研究这种潜在的调节能力,我们使用 Solexa 测序技术对在正常(28°C)和冷适应(10°C,10 天)条件下饲养的斑马鱼大脑中的 microRNAome 进行了表征。然后,我们使用 Affymetrix 斑马鱼基因组阵列分析检查了这两种条件下蛋白质编码基因的表达模式。通过各种统计分析,研究了 microRNAome 在斑马鱼大脑转录组冷调节中的潜在作用。
在 miRBase 网站(版本 16)上总共 214 个独特的成熟斑马鱼 miRNAs 中,本研究中回收了 175 个。此外,我们使用多种 miRNA 预测方法鉴定了 399 个新的成熟 miRNAs。我们定义了一组在冷和正常条件下差异表达的 25 个 miRNAs,并通过其靶基因的基因本体(GO)注释预测了它们所涉及的分子功能和生物过程。另一方面,微阵列分析表明,在冷应激中上调的基因中,与 mRNA 处理和应激反应相关的基因过表达,但与从差异 miRNAs 预测的任何 GO 分子功能和生物过程都没有直接对应。使用几种统计模型,包括一种新的基于网络的方法,我们发现,无论是单独使用还是共同使用,无论是直接还是间接(即通过转录因子介导),本研究中鉴定的 miRNAs 对低温条件下基因表达模式的变化只有很小的贡献。
我们的结果表明,mRNA 表达的冷应激反应可能主要通过 miRNA 介导的调节以外的调节模式来控制。动物大脑中的 miRNAs 可能更多地作为发育调节剂而不是热适应性调节剂。