2. Academic Validation
  3. NAP-seq reveals multiple classes of structured noncoding RNAs with regulatory functions

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

  • Nat Commun. 2024 Mar 18;15(1):2425. doi: 10.1038/s41467-024-46596-y.
Shurong Liu # 1,  Junhong Huang # 1 2,  Jie Zhou 1,  Siyan Chen 1 2,  Wujian Zheng 1,  Chang Liu 1,  Qiao Lin 1,  Ping Zhang 1,  Di Wu 1 2,  Simeng He 2,  Jiayi Ye 1,  Shun Liu 3,  Keren Zhou 4,  Bin Li 5,  Lianghu Qu 6,  Jianhua Yang 7 8
Affiliations

Affiliations

  • 1 MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, Guangdong, China.
  • 2 The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519082, Guangdong, China.
  • 3 Department of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
  • 4 Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA, 91016, USA.
  • 5 MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, Guangdong, China. [email protected].
  • 6 MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, Guangdong, China. [email protected].
  • 7 MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, Guangdong, China. [email protected].
  • 8 The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519082, Guangdong, China. [email protected].
  • # Contributed equally.
PMID: 38499544 DOI: 10.1038/s41467-024-46596-y
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.

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