Small nucleolar RNAs (snoRNAs) are structured noncoding RNAs present in multiple copies within eukaryotic genomes. snoRNAs guide chemical modifications on their target RNA and regulate processes like ribosome assembly and splicing. Most human snoRNAs are embedded within host gene introns, the remainder being independently expressed from intergenic regions. We recently characterized the abundance of snoRNAs and their host gene across several healthy human tissues and found that the level of most snoRNAs does not correlate with that of their host gene, with the observation that snoRNAs embedded within the same host gene often differ drastically in abundance. To better understand the determinants of snoRNA expression, we trained machine learning models to predict whether snoRNAs are expressed or not in human tissues based on more than 30 collected features related to snoRNAs and their genomic context. By interpreting the models’ predictions, we find that snoRNAs rely on conserved motifs, a stable global structure and terminal stem, and a transcribed locus to be expressed. We observe that these features explain well the varying abundance of snoRNAs embedded within the same host gene. By predicting the expression status of snoRNAs across several vertebrates, we notice that only one-third of all annotated snoRNAs are expressed per genome, as in humans. Our results suggest that ancestral snoRNAs disseminated within vertebrate genomes, sometimes leading to the development of new functions and a probable gain in fitness and thereby conserving features favorable to the expression of these few snoRNAs, the large remainder often degenerating into pseudogenes.

中文翻译：

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基序保护、稳定性和宿主基因表达是脊椎动物 snoRNA 表达的主要驱动力

小核仁 RNA (snoRNA) 是结构化的非编码 RNA，在真核生物基因组中以多个拷贝存在。snoRNAs 指导对其目标 RNA 进行化学修饰，并调节核糖体组装和剪接等过程。大多数人类 snoRNAs 嵌入宿主基因内含子中，其余的从基因间区域独立表达。我们最近对几个健康人体组织中 snoRNA 及其宿主基因的丰度进行了表征，发现大多数 snoRNA 的水平与其宿主基因的水平无关，观察到嵌入同一宿主基因中的 snoRNA 的丰度通常有很大差异. 为了更好地理解 snoRNA 表达的决定因素，我们训练了机器学习模型，根据收集到的 30 多个与 snoRNA 及其基因组背景相关的特征来预测 snoRNA 是否在人体组织中表达。通过解释模型的预测，我们发现 snoRNA 依赖于保守的基序、稳定的全局结构和末端茎，以及要表达的转录基因座。我们观察到这些特征很好地解释了嵌入同一宿主基因中的 snoRNA 的不同丰度。通过预测 snoRNA 在几种脊椎动物中的表达状态，我们注意到每个基因组仅表达所有带注释的 snoRNA 的三分之一，就像在人类中一样。我们的结果表明，祖先的 snoRNAs 在脊椎动物基因组中传播，