Sharova Lioudmila V, Sharov Alexei A, Nedorezov Timur, Piao Yulan, Shaik Nabeebi, Ko Minoru S H
Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA.
DNA Res. 2009 Feb;16(1):45-58. doi: 10.1093/dnares/dsn030. Epub 2008 Nov 11.
Degradation of mRNA is one of the key processes that control the steady-state level of gene expression. However, the rate of mRNA decay for the majority of genes is not known. We successfully obtained the rate of mRNA decay for 19 977 non-redundant genes by microarray analysis of RNA samples obtained from mouse embryonic stem (ES) cells. Median estimated half-life was 7.1 h and only <100 genes, including Prdm1, Myc, Gadd45 g, Foxa2, Hes5 and Trib1, showed half-life less than 1 h. In general, mRNA species with short half-life were enriched among genes with regulatory functions (transcription factors), whereas mRNA species with long half-life were enriched among genes related to metabolism and structure (extracellular matrix, cytoskeleton). The stability of mRNAs correlated more significantly with the structural features of genes than the function of genes: mRNA stability showed the most significant positive correlation with the number of exon junctions per open reading frame length, and negative correlation with the presence of PUF-binding motifs and AU-rich elements in 3'-untranslated region (UTR) and CpG di-nucleotides in the 5'-UTR. The mRNA decay rates presented in this report are the largest data set for mammals and the first for ES cells.
mRNA降解是控制基因表达稳态水平的关键过程之一。然而，大多数基因的mRNA衰减速率尚不清楚。我们通过对从小鼠胚胎干细胞（ES细胞）获得的RNA样本进行微阵列分析，成功获得了19977个非冗余基因的mRNA衰减速率。估计的中位半衰期为7.1小时，只有不到100个基因，包括Prdm1、Myc、Gadd45 g、Foxa2、Hes5和Trib1，半衰期小于1小时。一般来说，半衰期短的mRNA种类在具有调控功能的基因（转录因子）中富集，而半衰期长的mRNA种类在与代谢和结构相关的基因（细胞外基质、细胞骨架）中富集。mRNA的稳定性与基因的结构特征比与基因的功能更显著相关：mRNA稳定性与每个开放阅读框长度的外显子连接数呈最显著正相关，与3'-非翻译区（UTR）中PUF结合基序和富含AU元件以及5'-UTR中CpG二核苷酸的存在呈负相关。本报告中呈现的mRNA衰减速率是哺乳动物的最大数据集，也是ES细胞的首个数据集。
