Miller Justin B, Meurs Taylor E, Hodgman Matthew W, Song Benjamin, Miller Kyle N, Ebbert Mark T W, Kauwe John S K, Ridge Perry G
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40504, USA.
Department of Biology, Brigham Young University, Provo, UT 84602, USA.
NAR Genom Bioinform. 2022 May 30;4(2):lqac039. doi: 10.1093/nargab/lqac039. eCollection 2022 Jun.
Ramp sequences occur when the average translational efficiency of codons near the 5' end of highly expressed genes is significantly lower than the rest of the gene sequence, which counterintuitively increases translational efficiency by decreasing downstream ribosomal collisions. Here, we show that the relative codon adaptiveness within different tissues changes the existence of a ramp sequence without altering the underlying genetic code. We present the first comprehensive analysis of tissue and cell type-specific ramp sequences and report 3108 genes with ramp sequences that change between tissues and cell types, which corresponds with increased gene expression within those tissues and cells. The Ramp Atlas (https://ramps.byu.edu/) allows researchers to query precomputed ramp sequences in 18 388 genes across 62 tissues and 66 cell types and calculate tissue-specific ramp sequences from user-uploaded FASTA files through an intuitive web interface. We used The Ramp Atlas to identify seven SARS-CoV-2 genes and seven human SARS-CoV-2 entry factor genes with tissue-specific ramp sequences that may help explain viral proliferation within those tissues. We anticipate that The Ramp Atlas will facilitate personalized and creative tissue-specific ramp sequence analyses for both human and viral genes that will increase our ability to utilize this often-overlooked regulatory region.
当高表达基因5'端附近密码子的平均翻译效率显著低于基因序列的其余部分时,就会出现斜坡序列,这与直觉相反,它通过减少下游核糖体碰撞来提高翻译效率。在这里,我们表明不同组织内密码子的相对适应性改变了斜坡序列的存在,而不改变潜在的遗传密码。我们首次对组织和细胞类型特异性斜坡序列进行了全面分析,并报告了3108个具有斜坡序列的基因,这些基因在不同组织和细胞类型之间存在差异,这与这些组织和细胞内基因表达的增加相对应。斜坡图谱(https://ramps.byu.edu/)允许研究人员查询62种组织和66种细胞类型中18388个基因的预先计算的斜坡序列,并通过直观的网络界面从用户上传的FASTA文件中计算组织特异性斜坡序列。我们使用斜坡图谱鉴定了7个具有组织特异性斜坡序列的SARS-CoV-2基因和7个人类SARS-CoV-2进入因子基因,这些序列可能有助于解释病毒在这些组织中的增殖。我们预计,斜坡图谱将促进对人类和病毒基因进行个性化和创造性的组织特异性斜坡序列分析,这将提高我们利用这个经常被忽视的调控区域的能力。