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. Here, we systematically prof...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 117; no. 41; pp. 25634 - 25645
Main Authors Isakova, Alina, Fehlmann, Tobias, Keller, Andreas, Quake, Stephen R.
Format Journal Article
LanguageEnglish
Published Washington National Academy of Sciences 13.10.2020
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Summary: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. Here, we 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, we identified that ∼30% of small ncRNAs are distributed across the body in a tissue-specific manner with some also being sexually dimorphic. We 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, we 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, we 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 we expect that these data will be a resource for the further identification of ncRNAs involved in tissue function in health and dysfunction in disease.
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Reviewers: J.C.M., European Molecular Biology Laboratory–European Bioinformatics Institute; and I.U., Weizmann Institute of Science.
Author contributions: A.I. and S.R.Q. designed research; A.I. performed research; A.I., T.F., and A.K. analyzed data; and A.I. and S.R.Q. wrote the paper.
Contributed by Stephen R. Quake, July 29, 2020 (sent for review February 10, 2020; reviewed by John C. Marioni and Igor Ulitsky)
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.2002277117