NAP-seq reveals multiple classes of structured noncoding RNAs with regulatory functions

Shurong Liu, Junhong Huang, Jie Zhou, Siyan Chen, Wujian Zheng, Chang Liu, Qiao Lin, Ping Zhang, Di Wu, Simeng He, Jiayi Ye, Shun Liu, Keren Zhou, Bin Li (), Lianghu Qu () and Jianhua Yang ()
Additional contact information
Shurong Liu: Sun Yat-sen University
Junhong Huang: Sun Yat-sen University
Jie Zhou: Sun Yat-sen University
Siyan Chen: Sun Yat-sen University
Wujian Zheng: Sun Yat-sen University
Chang Liu: Sun Yat-sen University
Qiao Lin: Sun Yat-sen University
Ping Zhang: Sun Yat-sen University
Di Wu: Sun Yat-sen University
Simeng He: Sun Yat-sen University
Jiayi Ye: Sun Yat-sen University
Shun Liu: The University of Chicago
Keren Zhou: Beckman Research Institute of City of Hope
Bin Li: Sun Yat-sen University
Lianghu Qu: Sun Yat-sen University
Jianhua Yang: Sun Yat-sen University

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract Up to 80% of the human genome produces “dark matter” RNAs, most of which are noncapped RNAs (napRNAs) that frequently act as noncoding RNAs (ncRNAs) to modulate gene expression. Here, by developing a method, NAP-seq, to globally profile the full-length sequences of napRNAs with various terminal modifications at single-nucleotide resolution, we reveal diverse classes of structured ncRNAs. We discover stably expressed linear intron RNAs (sliRNAs), a class of snoRNA-intron RNAs (snotrons), a class of RNAs embedded in miRNA spacers (misRNAs) and thousands of previously uncharacterized structured napRNAs in humans and mice. These napRNAs undergo dynamic changes in response to various stimuli and differentiation stages. Importantly, we show that a structured napRNA regulates myoblast differentiation and a napRNA DINAP interacts with dyskerin pseudouridine synthase 1 (DKC1) to promote cell proliferation by maintaining DKC1 protein stability. Our approach establishes a paradigm for discovering various classes of ncRNAs with regulatory functions.

Date: 2024
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DOI: 10.1038/s41467-024-46596-y

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