Translocated in LipoSarcoma/Fused in Sarcoma (TLS/FUS) is a nuclear RNA binding protein whose mutations cause amyotrophic lateral sclerosis. TLS/FUS undergoes LLPS and forms membraneless particles with other proteins and nucleic acids. Interaction with RNA alters conformation of TLS/FUS, which affects binding with proteins, but the effect of mA RNA modification on the TLS/FUS-RNA interaction remains elusive. Here, we investigated the binding specificity of TLS/FUS to mA RNA fragments by RNA pull down assay, and elucidated that both wild type and ALS-related TLS/FUS mutants strongly bound to mA modified RNAs. TLS/FUS formed cytoplasmic foci by treating hyperosmotic stress, but the cells transfected with mA-modified RNAs had a smaller number of foci. Moreover, mA-modified RNA transfection resulted in the cells obtaining higher resistance to the stress. In summary, we propose TLS/FUS as a novel candidate of mA recognition protein, and mA-modified RNA fragments diffuse cytoplasmic TLS/FUS foci and thereby enhance cell viability.
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http://dx.doi.org/10.3390/ijms222011014 | DOI Listing |
Mol Cell
January 2025
Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, No. 155, Section 2, Li-nong Street, Taipei, Taiwan; Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, No. 155, Section 2, Li-nong Street, Taipei, Taiwan; Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, No. 155, Section 2, Li-nong Street, Taipei, Taiwan. Electronic address:
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Roger Williams Institute of Liver Studies, Foundation for Liver Research, London, UK.
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Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
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State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
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State Key Laboratory of Hybrid Rice, Laboratory of Plant Systematics and Evolutionary Biology, College of Life Sciences, Wuhan University, Wuhan, 430072, China.
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