A mouse tissue atlas of small noncoding RNA

Small noncoding RNAs (ncRNAs) play a vital role in a broad range of biological processes both in health and disease. A comprehensive quantitative reference of small ncRNA expression would significantly advance our understanding of ncRNA roles in shaping tissue functions. Stanford University researchers systematically profiled the levels of five ncRNA classes (microRNA [miRNA], small nucleolar RNA [snoRNA], small nuclear RNA [snRNA], small Cajal body-specific RNA [scaRNA], and transfer RNA [tRNA] fragments) across 11 mouse tissues by deep sequencing.

Using 14 biological replicates spanning both sexes, the researchers identified that ∼30% of small ncRNAs are distributed across the body in a tissue-specific manner with some also being sexually dimorphic. They found that some miRNAs are subject to “arm switching” between healthy tissues and that tRNA fragments are retained within tissues in both a gene- and a tissue-specific manner. Out of 11 profiled tissues, they confirmed that brain contains the largest number of unique small ncRNA transcripts, some of which were previously annotated while others are identified in this study. Furthermore, by combining these findings with single-cell chromatin accessibility (scATAC-seq) data, the researchers were able to connect identified brain-specific ncRNAs with their cell types of origin. These results yield the most comprehensive characterization of specific and ubiquitous small RNAs in individual murine tissues to date, and the authors expect that these data will be a resource for the further identification of ncRNAs involved in tissue function in health and dysfunction in disease.

Small ncRNA expression across mouse tissues

(A) Tissues and ncRNA classes profiled in the current study. Ten somatic tissues were collected from adult mice (n = 14). Testes were collected from male mice (n = 4). (B) ncRNAs identified in the current study. Numbers indicate detected and total annotated within GENCODE M20 miRNA, snoRNA, snRNA, scaRNA, Mt_tRNA, as well as high-confidence tRNA listed in GtRNAdb. (C) Coverage of ncRNA types within the profiled tissues. ncRNA was considered transcribed in a tissue if detected at >1 cpm. (D) Genomic map of small RNAs (sRNAs) expression across mouse genome. The bars show the log-transformed normalized expression count of ncRNAs. The red and gray bars around each circle represent the variance of each sRNA across 10 mouse tissues. Red denotes highly (the SD of expression above 25% of the mean value), and gray, low, variable ncRNAs (SD below 25% of the mean value).

Isakova A, Fehlmann T, Keller A, Quake SR. (2020) A mouse tissue atlas of small noncoding RNA. PNAS [epub ahead of print]. [article]

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