A dual effect of FUBP1 on SPA lncRNA maturation
- Zheng-Hu Yang1,2,
- Fang Nan3,
- Guang Xu1,
- Huang Wu1,
- Meng-Yuan Wei1,
- Li Yang3,
- Ling-Ling Chen1,2,4,5,6 and
- Hao Wu1
- 1Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
- 2School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
- 3Center for Molecular Medicine, Children's Hospital of Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
- 4School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
- 5New Cornerstone Science Laboratory, Shenzhen 518054, China
- 6Shanghai Academy of Natural Sciences (SANS), Shanghai 200031, China
- Corresponding author: wuhao2021{at}sibcb.ac.cn
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Handling editor: Fatima Gebauer
Abstract
SPAs are noncanonical long noncoding RNAs (lncRNAs) that are 5′ small nucleolar RNA (snoRNA) capped and 3′ polyadenylated. Two SPAs are processed from a polycistronic transcript embedded in the human 15q11-q13 region related to Prader–Willi syndrome (PWS). Once produced, SPAs accumulate at their transcription site and sequester splicing factors to form PWS bodies that are involved in alternative splicing regulation. But how the processing of SPAs is regulated has remained obscure. Here, we identified that both far upstream element-binding protein 1 (FUBP1) and myelin expression factor 2 (MYEF2) were enriched in the PWS bodies; loss of either individually impaired SPAs’ expression and dampened the size of PWS bodies in H9 and PA1 cells. Specifically, FUBP1, on the one hand, enhanced the transcription of SPA-embedded polycistronic transcripts by targeting the FUSE-like sequence upstream of the promoter, and on the other hand, was required for SPA1 splicing and maturation by binding the uridine (U)-rich intronic sequences. These findings suggest a comprehensive and distinct regulation of PWS region-derived SPA lncRNAs.
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Article is online at http://www.rnajournal.org/cgi/doi/10.1261/rna.080341.124.
- Received November 27, 2024.
- Accepted March 17, 2025.
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