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Exploring the expanding universe of small RNAs

Abstract

The world of small noncoding RNAs (sncRNAs) is ever-expanding, from small interfering RNA, microRNA and Piwi-interacting RNA to the recently emerging non-canonical sncRNAs derived from longer structured RNAs (for example, transfer, ribosomal, Y, small nucleolar, small nuclear and vault RNAs), showing distinct biogenesis and functional principles. Here we discuss recent tools for sncRNA identification, caveats in sncRNA expression analysis and emerging methods for direct sequencing of sncRNAs and systematic mapping of RNA modifications that are integral to their function.

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Fig. 1: Methods to overcome biases in sncRNA discovery and cautions in the interpretation of sncRNA-sequencing results.
Fig. 2: Two methods for future direct sequencing of RNA and multiplexed mapping of RNA modifications without cDNA intermediates.

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Acknowledgements

We thank P. Schimmel (The Scripps Research Institute), X. Chen (UC Riverside) and our laboratory members for critical discussions on the contents of the manuscript. Research in the Q.C. laboratory is in part supported by the National Institutes of Health (NIH grant nos R01HD092431, R01ES032024 and P50HD098593). The T.Z. laboratory is in part supported by the NIH (grant no. R01ES032024).

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Correspondence to Tong Zhou or Qi Chen.

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Shi, J., Zhou, T. & Chen, Q. Exploring the expanding universe of small RNAs. Nat Cell Biol 24, 415–423 (2022). https://doi.org/10.1038/s41556-022-00880-5

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