Compared to coding sequences, untranslated regions of the transcriptome are not well conserved, and functional annotation of these sequences is challenging. Global relationships between nucleotide composition of 3' UTR sequences and their sequence conservation have been appreciated since mammalian genomes were first sequenced, but the functional relevance of these patterns remain unknown. We systematically measured the effect on gene expression of the sequences of more than 25,000 RNA-binding protein (RBP) binding sites in primary mouse T cells using a massively parallel reporter assay. GC-rich sequences were destabilizing of reporter mRNAs and come from more rapidly evolving regions of the genome. These sequences were more likely to be folded in vivo and contain a number of structural motifs that reduced accumulation of a heterologous reporter protein. Comparison of full-length 3' UTR sequences across vertebrate phylogeny revealed that strictly conserved 3' UTRs were GC-poor and enriched in genes associated with organismal development. In contrast, rapidly evolving 3' UTRs tended to be GC-rich and derived from genes involved in metabolism and immune responses. Cell-essential genes had lower GC content in their 3' UTRs, suggesting a connection between unstructured mRNA noncoding sequences and optimal protein production. By reducing gene expression, GC-rich RBP-occupied sequences act as a rapidly evolving substrate for gene regulatory interactions.

中文翻译：

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大规模平行的3'UTR报告基因分析揭示了核苷酸含量，序列保守性和mRNA不稳定之间的关系。

与编码序列相比，转录组的非翻译区并不十分保守，这些序列的功能注释具有挑战性。自从哺乳动物基因组首次测序以来，人们已经意识到3'UTR序列的核苷酸组成与其序列保守性之间的全局关系，但是这些模式的功能相关性仍然未知。我们使用大规模平行报告基因分析系统地测量了原代小鼠T细胞中超过25,000个RNA结合蛋白（RBP）结合位点的序列对基因表达的影响。富含GC的序列使报告mRNA不稳定，并且来自基因组发展较快的区域。这些序列更可能在体内折叠，并且包含许多减少异源报道蛋白积累的结构基序。整个脊椎动物系统发育的全长3'UTR序列比较表明，严格保守的3'UTR缺乏GC，并且富含与机体发育相关的基因。相反，快速发展的3'UTR往往富含GC，并来源于与代谢和免疫反应有关的基因。细胞必需基因在其3'UTR中具有较低的GC含量，表明非结构化mRNA非编码序列与最佳蛋白质生产之间存在联系。通过减少基因表达，富含GC的RBP占据的序列充当了基因调控相互作用的快速进化底物。跨脊椎动物系统发育的UTR序列显示，严格保守的3'UTR缺乏GC，并且富含与机体发育相关的基因。相反，快速发展的3'UTR往往富含GC，并来源于与代谢和免疫反应有关的基因。细胞必需基因在其3'UTR中具有较低的GC含量，表明非结构化mRNA非编码序列与最佳蛋白质生产之间存在联系。通过减少基因表达，富含GC的RBP占据的序列充当了基因调控相互作用的快速进化底物。跨脊椎动物系统发育的UTR序列显示，严格保守的3'UTR缺乏GC，并且富含与机体发育相关的基因。相反，快速发展的3'UTR往往富含GC，并来源于与代谢和免疫反应有关的基因。细胞必需基因在其3'UTR中具有较低的GC含量，表明非结构化mRNA非编码序列与最佳蛋白质生产之间存在联系。通过减少基因表达，富含GC的RBP占据的序列充当了基因调控相互作用的快速进化底物。细胞必需基因在其3'UTR中具有较低的GC含量，表明非结构化mRNA非编码序列与最佳蛋白质生产之间存在联系。通过减少基因表达，富含GC的RBP占据的序列充当了基因调控相互作用的快速进化底物。细胞必需基因在其3'UTR中具有较低的GC含量，表明非结构化mRNA非编码序列与最佳蛋白质生产之间存在联系。通过减少基因表达，富含GC的RBP占据的序列充当了基因调控相互作用的快速进化底物。