Crossref journal-article
The Company of Biologists
Journal of Cell Science (237)
Abstract

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.

Bibliography

Zinszner, H., Sok, J., Immanuel, D., Yin, Y., & Ron, D. (1997). TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling. Journal of Cell Science, 110(15), 1741–1750.

Authors 5
  1. Helene Zinszner (first)
  2. John Sok (additional)
  3. David Immanuel (additional)
  4. Yin Yin (additional)
  5. David Ron (additional)
References 32 Referenced 284
  1. 10.1101/gad.8.4.453 / Genes Dev / CHOP (GADD153) and its oncogenic variant, TLS-CHOP, differ in their ability to induce G1/S arrest by Barone (1994)
  2. 10.1002/j.1460-2075.1996.tb00882.x / EMBO J / hTAFII68, a novel RNA/ssDNA-binding protein with homology to the pro-oncoproteins TLS/FUS and EWS is associated with both TFIID and RNA polymerase II by Bertolotti (1996)
  3. 10.1016/0168-9525(89)90100-5 / Trends Genet / How fixed is the differentiated state by Blau (1989)
  4. 10.1016/0092-8674(89)90241-9 / Cell / Major nucleolar proteins shuttle between the nucleus and cytoplasm by Borer (1989)
  5. 10.1126/science.8036511 / Science / Conserved structures and diversity of functions of RNA-binding proteins by Burd (1994)
  6. {'key': '2024010400343399100_JOCES_110_15_1741C6', 'first-page': '724', 'article-title': 'Identification of hnRNP P2 as TLS/FUS using electrospray mass spectrometry', 'volume': '1', 'author': 'Calvio', 'year': '1995', 'journal-title': 'RNA'} / RNA / Identification of hnRNP P2 as TLS/FUS using electrospray mass spectrometry by Calvio (1995)
  7. 10.1038/363640a0 / Nature / Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma with t(12;16)(q13;p11) by Crozat (1993)
  8. 10.1038/359162a0 / Nature / Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumors by Delattre (1992)
  9. {'key': '2024010400343399100_JOCES_110_15_1741C9', 'first-page': '415', 'article-title': 'Physical changes in cytoplasmic messenger ribonucleoproteins in cells treated with inhibitors of mRNA transcription', 'volume': '4', 'author': 'Dreyfuss', 'year': '1984', 'journal-title': 'Mol. Cell. Biol'} / Mol. Cell. Biol / Physical changes in cytoplasmic messenger ribonucleoproteins in cells treated with inhibitors of mRNA transcription by Dreyfuss (1984)
  10. 10.1073/pnas.80.6.1599 / Proc. Nat. Acad. Sci. USA / Structure of nuclear ribonucleoprotein: heterogenous nuclear RNA is complexed with a major sextet of proteins in vivo by Economidis (1983)
  11. {'key': '2024010400343399100_JOCES_110_15_1741C11', 'first-page': '421', 'article-title': 'The RNP motif protein family', 'volume': '4', 'author': 'Haynes', 'year': '1992', 'journal-title': 'New Biol'} / New Biol / The RNP motif protein family by Haynes (1992)
  12. 10.1128/MCB.15.8.4562 / Mol. Cell. Biol / Association of SARFH (sarcoma associated RNA-binding fly homologue), with regions of chromatin transcribed by RNA polymerase II by Immanuel (1995)
  13. 10.1016/0968-0004(91)90088-D / Trends Biochem. Sci / RNA recognition: towards identifying determinants of specificity by Kenan (1991)
  14. 10.1083/jcb.116.2.257 / J. Cell Biol / Drosophila heterogenous nuclear ribonucleoproteins by Matunis (1992)
  15. 10.1073/pnas.90.12.5752 / Proc. Nat. Acad. Sci. USA / Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation by May (1993)
  16. {'key': '2024010400343399100_JOCES_110_15_1741C16', 'first-page': '7393', 'article-title': 'The Ewing’s sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1', 'volume': '13', 'author': 'May', 'year': '1993', 'journal-title': 'Mol. Cell. Biol'} / Mol. Cell. Biol / The Ewing’s sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1 by May (1993)
  17. 10.1038/385357a0 / Nature / The C-terminal domain of RNA polymerase II couples mRNA processing to transcription by McCracken (1997)
  18. 10.1016/0092-8674(95)90119-1 / Cell / A nuclear export signal in hnRNP A1: A signal mediated, temperature-dependent nuclear protein export pathway by Michael (1995)
  19. {'key': '2024010400343399100_JOCES_110_15_1741C19', 'first-page': '3087', 'article-title': 'The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round tumors, codes for an RNA binding proteins with novel regulatory domains', 'volume': '9', 'author': 'Ohno', 'year': '1994', 'journal-title': 'Oncogene'} / Oncogene / The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round tumors, codes for an RNA binding proteins with novel regulatory domains by Ohno (1994)
  20. 10.1038/355730a0 / Nature / Shuttling of pre-mRNA binding proteins between the nucleus and cytoplasm by Pinol-Roma (1992)
  21. 10.1016/0962-8924(93)90135-N / Trends Cell Biol / hnRNP proteins: localization and transport between the nucleus and the cytoplasm by Pinol-Roma (1993)
  22. {'key': '2024010400343399100_JOCES_110_15_1741C22', 'first-page': '3717', 'article-title': 'TLS/FUS fusion domain of TLS/FUS-erg chimeric protein resulting from the t(16;21) chromosomal translocation in human myeloid leukemia functions as a transcriptional activation domain', 'volume': '9', 'author': 'Prasad', 'year': '1994', 'journal-title': 'Oncogene'} / Oncogene / TLS/FUS fusion domain of TLS/FUS-erg chimeric protein resulting from the t(16;21) chromosomal translocation in human myeloid leukemia functions as a transcriptional activation domain by Prasad (1994)
  23. 10.1038/372143a0 / Nature / Chromosomal translocations in human cancer by Rabbitts (1994)
  24. {'key': '2024010400343399100_JOCES_110_15_1741C24', 'first-page': '131', 'article-title': 'TLS-CHOP and the role of RNA-binding proteins in oncogenic transformation', 'volume-title': 'In Chromosomal Translocations and Oncogenic Transcription Factors', 'author': 'Ron', 'year': '1996'} / In Chromosomal Translocations and Oncogenic Transcription Factors / TLS-CHOP and the role of RNA-binding proteins in oncogenic transformation by Ron (1996)
  25. 10.1073/pnas.91.17.7869 / Proc. Nat. Acad. Sci. USA / Transcriptional activation by TAL1 and FUS-CHOP proteins expressed in acute malignancies as a result of chrmosomal abnormalities by Sanchez-Garciá (1994)
  26. 10.1093/nar/17.15.6419 / Nucl. Acids Res / Rapid detection of octamer binding proteins with ‘mini-extracts’, prepared from a small number of cells by Schreiber (1989)
  27. 10.1093/nar/23.5.835 / Nucl. Acids Res / Cabeza, a Drosophila gene encoding a novel RNA binding protein, shares homology with EWS and TLS, two genes involved in human sarcoma formation by Stolow (1995)
  28. 10.1093/nar/10.10.3039 / Nucl. Acid Res / Detection of a cellular polypeptide associated with adenovirus-coded VA RNA using in vitro labeling of proteins cross-linked to RNA by van Eekelen (1982)
  29. 10.1016/S0092-8674(00)80980-0 / Cell / A pre-mRNA-binding protein accompanies the RNA from the gene through the nuclear pores and into polysomes by Visa (1996)
  30. 10.1111/j.1432-1033.1980.tb07207.x / Eur. J. Biochem / Cross-linking of mRNA to proteins by irradiation of intact cells with ultraviolet light by Wagenmakers (1980)
  31. 10.1101/gad.8.21.2513 / Genes Dev / A novel effector domain from the RNA-binding proteins TLS or EWS is required for oncogenic transformation by CHOP by Zinszner (1994)
  32. 10.1038/sj.onc.1200854 / Oncogene / A topogenic role for the N terminus of TLS: nucleolar localization when transcription is inhibited by Zinszner (1997)
Dates
Type When
Created 4 years, 4 months ago (April 25, 2021, 12:47 p.m.)
Deposited 1 year, 8 months ago (Jan. 3, 2024, 7:35 p.m.)
Indexed 4 weeks, 2 days ago (Aug. 6, 2025, 8:54 a.m.)
Issued 28 years, 1 month ago (Aug. 1, 1997)
Published 28 years, 1 month ago (Aug. 1, 1997)
Published Online 28 years, 1 month ago (Aug. 1, 1997)
Published Print 28 years, 1 month ago (Aug. 1, 1997)
Funders 0

None

@article{Zinszner_1997, title={TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling}, volume={110}, ISSN={1477-9137}, url={http://dx.doi.org/10.1242/jcs.110.15.1741}, DOI={10.1242/jcs.110.15.1741}, number={15}, journal={Journal of Cell Science}, publisher={The Company of Biologists}, author={Zinszner, Helene and Sok, John and Immanuel, David and Yin, Yin and Ron, David}, year={1997}, month=aug, pages={1741–1750} }