Shabalina Svetlana A, Ogurtsov Aleksey Y, Lipman David J, Kondrashov Alexey S
National Center for Biotechnology Information, National Institutes of Health, 8600 Rockville Pike, Building 38A, Bethesda, MD 20894, USA.
Nucleic Acids Res. 2003 Sep 15;31(18):5433-9. doi: 10.1093/nar/gkg751.
Post-transcriptional regulation and the formation of mRNA 3' ends are crucial for gene expression in eukaryotes. Interspecies conservation of many sequences within 3'UTRs reveals selective constraint due to similar function. To study the pattern of conservation within 3'UTRs, we compiled and aligned 50 sets of complete orthologous 3'UTRs from four orders of mammals. We observed a mosaic pattern of conservation, with alternating regions of high (phylogenetic footprints) and low similarity. Conservation in 3'UTRs correlates with their base composition and also with the synonymous substitution rate in corresponding coding regions. The non-uniform distribution of conservation is more pronounced for 3'UTRs with a moderate or low level of overall conservation, where invariant nucleotides are more numerous, and their runs of lengths 4-7 occur more frequently than if conservation were random. Many runs of invariant nucleotides are AU-rich or pyrimidine-rich. Some of these runs coincide with known functional cis- elements of eukaryotic mRNAs, such as the U-rich upstream element, polyadenylation signal and DICE regulatory signal. More divergent regions of multiple alignments of 3'UTRs are often more G- and/or C-rich. Our results provide evidence on the importance of moderately conserved regions in 3'UTRs and suggest that regulatory functions of 3'UTRs might utilize gene-specific information in these regions.
转录后调控以及mRNA 3'末端的形成对于真核生物中的基因表达至关重要。3'非翻译区（3'UTR）内许多序列的种间保守性揭示了由于功能相似而产生的选择性限制。为了研究3'UTR内的保守模式，我们汇编并比对了来自四个哺乳动物目50组完整的直系同源3'UTR。我们观察到一种镶嵌式的保守模式，即高相似性（系统发育足迹）和低相似性区域交替出现。3'UTR中的保守性与其碱基组成相关，也与相应编码区的同义替换率相关。对于整体保守程度为中等或较低水平的3'UTR，保守性的非均匀分布更为明显，其中不变核苷酸数量更多，并且长度为4 - 7的连续不变核苷酸序列出现的频率高于保守性为随机情况时。许多连续不变核苷酸序列富含AU或富含嘧啶。其中一些序列与真核生物mRNA已知的功能性顺式元件重合，如富含U的上游元件、多聚腺苷酸化信号和DICE调控信号。3'UTR多重比对中差异较大的区域通常富含G和/或C。我们的结果证明了3'UTR中适度保守区域的重要性，并表明3'UTR的调控功能可能利用了这些区域中的基因特异性信息。
