BACKGROUND The advent of next generation sequencing (NGS) has allowed the discovery of short and long non-coding RNAs (ncRNAs) in an unbiased manner using reverse genetics approaches, enabling the discovery of multiple categories of ncRNAs and characterization of the way their expression is regulated. We previously showed that the identities and abundances of microRNA isoforms (isomiRs) and transfer RNA-derived fragments (tRFs) are tightly regulated, and that they depend on a person's sex and population origin, as well as on tissue type, tissue state, and disease type. Here, we characterize the regulation and distribution of fragments derived from ribosomal RNAs (rRNAs). rRNAs form a group that includes four (5S, 5.8S, 18S, 28S) rRNAs encoded by the human nuclear genome and two (12S, 16S) by the mitochondrial genome. rRNAs constitute the most abundant RNA type in eukaryotic cells. RESULTS We analyzed rRNA-derived fragments (rRFs) across 434 transcriptomic datasets obtained from lymphoblastoid cell lines (LCLs) derived from healthy participants of the 1000 Genomes Project. The 434 datasets represent five human populations and both sexes. We examined each of the six rRNAs and their respective rRFs, and did so separately for each population and sex. Our analysis shows that all six rRNAs produce rRFs with unique identities, normalized abundances, and lengths. The rRFs arise from the 5'-end (5'-rRFs), the interior (i-rRFs), and the 3'-end (3'-rRFs) or straddle the 5' or 3' terminus of the parental rRNA (x-rRFs). Notably, a large number of rRFs are produced in a population-specific or sex-specific manner. Preliminary evidence suggests that rRF production is also tissue-dependent. Of note, we find that rRF production is not affected by the identity of the processing laboratory or the library preparation kit. CONCLUSIONS Our findings suggest that rRFs are produced in a regimented manner by currently unknown processes that are influenced by both ubiquitous as well as population-specific and sex-specific factors. The properties of rRFs mirror the previously reported properties of isomiRs and tRFs and have implications for the study of homeostasis and disease.

中文翻译：

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核糖体RNA片段化成短RNA（rRF）的方式是按性别和种群特异性来进行的。

背景技术下一代测序（NGS）的出现允许使用反向遗传学方法以无偏见的方式发现长短的非编码RNA（ncRNA），从而能够发现多种类别的ncRNA并表征其表达方式。规范的。我们之前曾证明，microRNA亚型（isomiRs）和源自RNA的转移片段（tRF）的身份和丰富度受到严格监管，并且它们取决于人的性别和人口起源以及组织类型，组织状态和疾病类型。在这里，我们表征核糖体RNA（rRNA）衍生的片段的调节和分布。rRNA组成一个组，其中包括由人核基因组编码的四个（5S，5.8S，18S，28S）rRNA和由线粒体基因组编码的两个（12S，16S）。rRNA构成真核细胞中最丰富的RNA类型。结果我们分析了434个转录组数据集的rRNA衍生片段（rRF），这些数据集来自1000个基因组计划健康参与者的淋巴母细胞系（LCL）。434个数据集代表五个人口和性别。我们检查了六个rRNA的每一个及其各自的rRF，并分别针对每个人群和性别进行了检查。我们的分析表明，所有六个rRNA产生的rRF具有唯一的身份，标准化的丰度和长度。rRF源自亲本rRNA的5'端（5'-rRF），内部（i-rRF）和3'端（3'-rRF）或跨在亲本rRNA的5'或3'末端（ x-rRF）。值得注意的是，大量的rRF以特定于人群或特定于性别的方式产生。初步证据表明，rRF的产生也是组织依赖性的。值得注意的是，我们发现rRF的生产不受加工实验室或文库制备试剂盒的影响。结论我们的研究结果表明，rRFs是由目前未知的过程以有序的方式产生的，该过程受普遍存在的以及人群特异性和性别特异性因素的影响。rRFs的特性反映了先前报道的isoomiRs和tRFs的特性，对稳态和疾病的研究具有重要意义。结论我们的研究结果表明，rRFs是由目前未知的过程以有序的方式产生的，该过程受普遍存在的以及人群特异性和性别特异性因素的影响。rRFs的特性反映了先前报道的isoomiRs和tRFs的特性，对稳态和疾病的研究具有重要意义。结论我们的研究结果表明，rRFs是由目前未知的过程以有序的方式产生的，该过程受普遍存在的以及人群特异性和性别特异性因素的影响。rRFs的特性反映了先前报道的isoomiRs和tRFs的特性，对稳态和疾病的研究具有重要意义。