Cited by 350RNA Research and SplicingNuclear Structure and FunctionSarcoma Diagnosis and Treatment

TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling

Zinszner, Helene, Sok, John, Immanuel, David, Yin, Yin, Ron, David·1997·Journal of Cell Science

Abstract

TLS, the product of a gene commonly translocated in liposarcomas (TLS), is prototypical of a newly identified class of nuclear proteins that contain a C-terminal domain with a distinct RNA recognition motif (RRM) surrounded by Arg-Gly-Gly (RGG) repeats. Its unique N terminus serves as an essential transforming domain for a number of fusion oncoproteins in human sarcomas and leukemias. In this study we use an in vivo UV crosslinking procedure to probe the interactions of TLS with RNA. TLS is found to bind RNA in vivo and the association of TLS with RNA is rapidly diminished by treating cells with transcriptional inhibitors. This suggests that the species bound by TLS turns over rapidly. Surprisingly, the RRM was found to be dispensable for RNA binding by TLS in vivo, suggesting that at any one time most of the interactions between TLS and RNA in the cell are not sequence specific. Analysis of inter specific heterokaryons formed between human and mouse or Xenopus cells revealed that TLS engages in rapid nucleocytoplasmic shuttling, a finding confirmed by the ability of anti-TLS antibodies to trap TLS when injected into the cytoplasm of HeLa cells. Cellular fractionation experiments suggest that TLS binds to RNA in both the nucleus and cytoplasm and support the hypothesis that TLS functions as a heterogeneous ribonuclear protein (hnRNP)-like chaperone of RNA. These findings are discussed in the context of the role altered forms of TLS play in cellular transformation.

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Crossref · 10.1242/jcs.110.15.1741

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  • FUS is a widely expressed, predominantly nuclear RNA-binding protein.

    “Another ALS and FTLD gene, FUS156, is a widely expressed, predominantly nuclear RNA-binding protein176,177”

    From The neurogenetics of alternative splicing (2016) · cites this paper as [177]

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Authors
Zinszner, H., Sok, J., Immanuel, D., Yin, Y., & Ron, D.
Affiliations
  • Skirball Institute of Biomolecular Medicine, the Departments of Medicine, Cell Biology and the Kaplan Cancer Center, NYU Medical Center, New York, NY 10016, USA
  • NYU Langone Health (US)
Venue
Journal of Cell Science
Published
1997-08-01
Volume
110
Issue
15
Pages
1741-1750
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
OpenAlex
W2115670698
Cited by
350
References
36
Citations by year
2026: 2 · 2025: 12 · 2024: 5 · 2023: 14 · 2022: 17 · 2021: 19 · 2020: 22 · 2019: 13 · 2018: 21 · 2017: 14 · 2016: 18 · 2015: 15 · 2014: 18 · 2013: 17 · 2012: 29
FWCI
1.90
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Cell Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ca060945-09)
  • National Cancer Institute (CA-60945)
  • National Institute of General Medical Sciences (5T32GM07038)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
Keywords
TLS, RNA recognition motif, RNA binding, nucleocytoplasmic shuttling, fusion oncoproteins, cell transformation, transcription inhibitors, heterokaryons, UV crosslinking
MeSH terms
Animals, Cell Nucleus, Centrifugation, Density Gradient, Cytoplasm, Dactinomycin, HeLa Cells, Humans, Ribonucleoproteins, RNA, Ultraviolet Rays, Xenopus, RNA-Binding Proteins, Coculture Techniques, Nucleic Acid Synthesis Inhibitors, COS Cells, Heterogeneous-Nuclear Ribonucleoproteins, RNA-Binding Protein FUS, Mice

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