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REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export.

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  • 1. Institute of Microbiology, Lausanne, Switzerland.
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    • Stutz F 1
    (1 author)

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RNA (New York, N.Y.), 01 Apr 2000, 6(4):638-650
https://doi.org/10.1017/s1355838200000078 PMID: 10786854 PMCID: PMC1369944

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Abstract 

Vertebrate TAP and its yeast ortholog Mex67p are involved in the export of messenger RNAs from the nucleus. TAP has also been implicated in the export of simian type D viral RNAs bearing the constitutive transport element (CTE). Although TAP directly interacts with CTE-bearing RNAs, the mode of interaction of TAP/Mex67p with cellular mRNAs is different from that with the CTE RNA and is likely to be mediated by protein-protein interactions. Here we show that Mex67p directly interacts with Yra1p, an essential yeast hnRNP-like protein. This interaction is evolutionarily conserved as Yra1p also interacts with TAP. Conditional expression in yeast cells implicates Yra1 p in the export of cellular mRNAs. Database searches revealed that Yra1p belongs to an evolutionarily conserved family of hnRNP-like proteins having more than one member in Mus musculus, Xenopus laevis, Caenorhabditis elegans, and Schizosaccharomyces pombe and at least one member in several species including plants. The murine members of the family directly interact with TAP. Because members of this protein family are characterized by the presence of one RNP-motif RNA-binding domain and exhibit RNA-binding activity, we called these proteins REF-bps for RNA and export factor binding proteins. Thus, Yra1p and members of the REF family of hnRNP-like proteins may facilitate the interaction of TAP/Mex67p with cellular mRNAs.

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RNA. 2000 Apr; 6(4): 638–650.
PMCID: PMC1369944
PMID: 10786854

REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export.

F Stutz, A Bachi, T Doerks, I C Braun, B Séraphin, M Wilm, P Bork, and E Izaurralde
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Abstract

Vertebrate TAP and its yeast ortholog Mex67p are involved in the export of messenger RNAs from the nucleus. TAP has also been implicated in the export of simian type D viral RNAs bearing the constitutive transport element (CTE). Although TAP directly interacts with CTE-bearing RNAs, the mode of interaction of TAP/Mex67p with cellular mRNAs is different from that with the CTE RNA and is likely to be mediated by protein-protein interactions. Here we show that Mex67p directly interacts with Yra1p, an essential yeast hnRNP-like protein. This interaction is evolutionarily conserved as Yra1p also interacts with TAP. Conditional expression in yeast cells implicates Yra1 p in the export of cellular mRNAs. Database searches revealed that Yra1p belongs to an evolutionarily conserved family of hnRNP-like proteins having more than one member in Mus musculus, Xenopus laevis, Caenorhabditis elegans, and Schizosaccharomyces pombe and at least one member in several species including plants. The murine members of the family directly interact with TAP. Because members of this protein family are characterized by the presence of one RNP-motif RNA-binding domain and exhibit RNA-binding activity, we called these proteins REF-bps for RNA and export factor binding proteins. Thus, Yra1p and members of the REF family of hnRNP-like proteins may facilitate the interaction of TAP/Mex67p with cellular mRNAs.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. [Europe PMC free article] [Abstract] [Google Scholar]
  • Bachi A, Braun IC, Rodrigues JP, Panté N, Ribbeck K, von Kobbe C, Kutay U, Wilm M, Görlich D, Carmo-Fonseca M, et al. The C-terminal domain of TAP interacts with the nuclear pore complex and promotes export of specific CTE-bearing RNA substrates. RNA. 2000 Jan;6(1):136–158. [Europe PMC free article] [Abstract] [Google Scholar]
  • Bear J, Tan W, Zolotukhin AS, Tabernero C, Hudson EA, Felber BK. Identification of novel import and export signals of human TAP, the protein that binds to the constitutive transport element of the type D retrovirus mRNAs. Mol Cell Biol. 1999 Sep;19(9):6306–6317. [Europe PMC free article] [Abstract] [Google Scholar]
  • Birney E, Thompson JD, Gibson TJ. PairWise and SearchWise: finding the optimal alignment in a simultaneous comparison of a protein profile against all DNA translation frames. Nucleic Acids Res. 1996 Jul 15;24(14):2730–2739. [Europe PMC free article] [Abstract] [Google Scholar]
  • Bharathi A, Ghosh A, Whalen WA, Yoon JH, Pu R, Dasso M, Dhar R. The human RAE1 gene is a functional homologue of Schizosaccharomyces pombe rae1 gene involved in nuclear export of Poly(A)+ RNA. Gene. 1997 Oct 1;198(1-2):251–258. [Abstract] [Google Scholar]
  • Braun IC, Rohrbach E, Schmitt C, Izaurralde E. TAP binds to the constitutive transport element (CTE) through a novel RNA-binding motif that is sufficient to promote CTE-dependent RNA export from the nucleus. EMBO J. 1999 Apr 1;18(7):1953–1965. [Europe PMC free article] [Abstract] [Google Scholar]
  • Brown JA, Bharathi A, Ghosh A, Whalen W, Fitzgerald E, Dhar R. A mutation in the Schizosaccharomyces pombe rae1 gene causes defects in poly(A)+ RNA export and in the cytoskeleton. J Biol Chem. 1995 Mar 31;270(13):7411–7419. [Abstract] [Google Scholar]
  • Bruhn L, Munnerlyn A, Grosschedl R. ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function. Genes Dev. 1997 Mar 1;11(5):640–653. [Abstract] [Google Scholar]
  • Burd CG, Dreyfuss G. Conserved structures and diversity of functions of RNA-binding proteins. Science. 1994 Jul 29;265(5172):615–621. [Abstract] [Google Scholar]
  • Doye V, Wepf R, Hurt EC. A novel nuclear pore protein Nup133p with distinct roles in poly(A)+ RNA transport and nuclear pore distribution. EMBO J. 1994 Dec 15;13(24):6062–6075. [Europe PMC free article] [Abstract] [Google Scholar]
  • Gabler S, Schütt H, Groitl P, Wolf H, Shenk T, Dobner T. E1B 55-kilodalton-associated protein: a cellular protein with RNA-binding activity implicated in nucleocytoplasmic transport of adenovirus and cellular mRNAs. J Virol. 1998 Oct;72(10):7960–7971. [Europe PMC free article] [Abstract] [Google Scholar]
  • Galtier N, Gouy M, Gautier C. SEAVIEW and PHYLO_WIN: two graphic tools for sequence alignment and molecular phylogeny. Comput Appl Biosci. 1996 Dec;12(6):543–548. [Abstract] [Google Scholar]
  • Görlich D, Kutay U. Transport between the cell nucleus and the cytoplasm. Annu Rev Cell Dev Biol. 1999;15:607–660. [Abstract] [Google Scholar]
  • Grüter P, Tabernero C, von Kobbe C, Schmitt C, Saavedra C, Bachi A, Wilm M, Felber BK, Izaurralde E. TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol Cell. 1998 Apr;1(5):649–659. [Abstract] [Google Scholar]
  • Javerzat JP, Cranston G, Allshire RC. Fission yeast genes which disrupt mitotic chromosome segregation when overexpressed. Nucleic Acids Res. 1996 Dec 1;24(23):4676–4683. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kadowaki T, Hitomi M, Chen S, Tartakoff AM. Nuclear mRNA accumulation causes nucleolar fragmentation in yeast mtr2 mutant. Mol Biol Cell. 1994 Nov;5(11):1253–1263. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kang Y, Cullen BR. The human Tap protein is a nuclear mRNA export factor that contains novel RNA-binding and nucleocytoplasmic transport sequences. Genes Dev. 1999 May 1;13(9):1126–1139. [Europe PMC free article] [Abstract] [Google Scholar]
  • Katahira J, Strässer K, Podtelejnikov A, Mann M, Jung JU, Hurt E. The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human. EMBO J. 1999 May 4;18(9):2593–2609. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kessler MM, Henry MF, Shen E, Zhao J, Gross S, Silver PA, Moore CL. Hrp1, a sequence-specific RNA-binding protein that shuttles between the nucleus and the cytoplasm, is required for mRNA 3'-end formation in yeast. Genes Dev. 1997 Oct 1;11(19):2545–2556. [Europe PMC free article] [Abstract] [Google Scholar]
  • Kraemer D, Blobel G. mRNA binding protein mrnp 41 localizes to both nucleus and cytoplasm. Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9119–9124. [Europe PMC free article] [Abstract] [Google Scholar]
  • Lee MS, Henry M, Silver PA. A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export. Genes Dev. 1996 May 15;10(10):1233–1246. [Abstract] [Google Scholar]
  • Longtine MS, McKenzie A, 3rd, Demarini DJ, Shah NG, Wach A, Brachat A, Philippsen P, Pringle JR. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast. 1998 Jul;14(10):953–961. [Abstract] [Google Scholar]
  • Mattaj IW, Englmeier L. Nucleocytoplasmic transport: the soluble phase. Annu Rev Biochem. 1998;67:265–306. [Abstract] [Google Scholar]
  • Murphy R, Watkins JL, Wente SR. GLE2, a Saccharomyces cerevisiae homologue of the Schizosaccharomyces pombe export factor RAE1, is required for nuclear pore complex structure and function. Mol Biol Cell. 1996 Dec;7(12):1921–1937. [Europe PMC free article] [Abstract] [Google Scholar]
  • Murphy R, Wente SR. An RNA-export mediator with an essential nuclear export signal. Nature. 1996 Sep 26;383(6598):357–360. [Abstract] [Google Scholar]
  • Nagai K, Oubridge C, Ito N, Avis J, Evans P. The RNP domain: a sequence-specific RNA-binding domain involved in processing and transport of RNA. Trends Biochem Sci. 1995 Jun;20(6):235–240. [Abstract] [Google Scholar]
  • Nakielny S, Dreyfuss G. Transport of proteins and RNAs in and out of the nucleus. Cell. 1999 Dec 23;99(7):677–690. [Abstract] [Google Scholar]
  • Pasquinelli AE, Ernst RK, Lund E, Grimm C, Zapp ML, Rekosh D, Hammarskjöld ML, Dahlberg JE. The constitutive transport element (CTE) of Mason-Pfizer monkey virus (MPMV) accesses a cellular mRNA export pathway. EMBO J. 1997 Dec 15;16(24):7500–7510. [Europe PMC free article] [Abstract] [Google Scholar]
  • Piñol-Roma S, Swanson MS, Matunis MJ, Dreyfuss G. Purification and characterization of proteins of heterogeneous nuclear ribonucleoprotein complexes by affinity chromatography. Methods Enzymol. 1990;181:326–331. [Abstract] [Google Scholar]
  • Portman DS, Dreyfuss G. RNA annealing activities in HeLa nuclei. EMBO J. 1994 Jan 1;13(1):213–221. [Europe PMC free article] [Abstract] [Google Scholar]
  • Portman DS, O'Connor JP, Dreyfuss G. YRA1, an essential Saccharomyces cerevisiae gene, encodes a novel nuclear protein with RNA annealing activity. RNA. 1997 May;3(5):527–537. [Europe PMC free article] [Abstract] [Google Scholar]
  • Pritchard CE, Fornerod M, Kasper LH, van Deursen JM. RAE1 is a shuttling mRNA export factor that binds to a GLEBS-like NUP98 motif at the nuclear pore complex through multiple domains. J Cell Biol. 1999 Apr 19;145(2):237–254. [Europe PMC free article] [Abstract] [Google Scholar]
  • Puig O, Rutz B, Luukkonen BG, Kandels-Lewis S, Bragado-Nilsson E, Séraphin B. New constructs and strategies for efficient PCR-based gene manipulations in yeast. Yeast. 1998 Sep 15;14(12):1139–1146. [Abstract] [Google Scholar]
  • Rigaut G, Shevchenko A, Rutz B, Wilm M, Mann M, Séraphin B. A generic protein purification method for protein complex characterization and proteome exploration. Nat Biotechnol. 1999 Oct;17(10):1030–1032. [Abstract] [Google Scholar]
  • Rost B, Sander C, Schneider R. PHD--an automatic mail server for protein secondary structure prediction. Comput Appl Biosci. 1994 Feb;10(1):53–60. [Abstract] [Google Scholar]
  • Saavedra C, Felber B, Izaurralde E. The simian retrovirus-1 constitutive transport element, unlike the HIV-1 RRE, uses factors required for cellular mRNA export. Curr Biol. 1997 Sep 1;7(9):619–628. [Abstract] [Google Scholar]
  • Santos-Rosa H, Moreno H, Simos G, Segref A, Fahrenkrog B, Panté N, Hurt E. Nuclear mRNA export requires complex formation between Mex67p and Mtr2p at the nuclear pores. Mol Cell Biol. 1998 Nov;18(11):6826–6838. [Europe PMC free article] [Abstract] [Google Scholar]
  • Schmitt C, von Kobbe C, Bachi A, Panté N, Rodrigues JP, Boscheron C, Rigaut G, Wilm M, Séraphin B, Carmo-Fonseca M, et al. Dbp5, a DEAD-box protein required for mRNA export, is recruited to the cytoplasmic fibrils of nuclear pore complex via a conserved interaction with CAN/Nup159p. EMBO J. 1999 Aug 2;18(15):4332–4347. [Europe PMC free article] [Abstract] [Google Scholar]
  • Segref A, Sharma K, Doye V, Hellwig A, Huber J, Lührmann R, Hurt E. Mex67p, a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores. EMBO J. 1997 Jun 2;16(11):3256–3271. [Europe PMC free article] [Abstract] [Google Scholar]
  • Scherly D, Boelens W, van Venrooij WJ, Dathan NA, Hamm J, Mattaj IW. Identification of the RNA binding segment of human U1 A protein and definition of its binding site on U1 snRNA. EMBO J. 1989 Dec 20;8(13):4163–4170. [Europe PMC free article] [Abstract] [Google Scholar]
  • Shevchenko A, Wilm M, Vorm O, Mann M. Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal Chem. 1996 Mar 1;68(5):850–858. [Abstract] [Google Scholar]
  • Snay-Hodge CA, Colot HV, Goldstein AL, Cole CN. Dbp5p/Rat8p is a yeast nuclear pore-associated DEAD-box protein essential for RNA export. EMBO J. 1998 May 1;17(9):2663–2676. [Europe PMC free article] [Abstract] [Google Scholar]
  • Strahm Y, Fahrenkrog B, Zenklusen D, Rychner E, Kantor J, Rosbach M, Stutz F. The RNA export factor Gle1p is located on the cytoplasmic fibrils of the NPC and physically interacts with the FG-nucleoporin Rip1p, the DEAD-box protein Rat8p/Dbp5p and a new protein Ymr 255p. EMBO J. 1999 Oct 15;18(20):5761–5777. [Europe PMC free article] [Abstract] [Google Scholar]
  • Stutz F, Kantor J, Zhang D, McCarthy T, Neville M, Rosbash M. The yeast nucleoporin rip1p contributes to multiple export pathways with no essential role for its FG-repeat region. Genes Dev. 1997 Nov 1;11(21):2857–2868. [Europe PMC free article] [Abstract] [Google Scholar]
  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res. 1997 Dec 15;25(24):4876–4882. [Europe PMC free article] [Abstract] [Google Scholar]
  • Tseng SS, Weaver PL, Liu Y, Hitomi M, Tartakoff AM, Chang TH. Dbp5p, a cytosolic RNA helicase, is required for poly(A)+ RNA export. EMBO J. 1998 May 1;17(9):2651–2662. [Europe PMC free article] [Abstract] [Google Scholar]
  • Watkins JL, Murphy R, Emtage JL, Wente SR. The human homologue of Saccharomyces cerevisiae Gle1p is required for poly(A)+ RNA export. Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6779–6784. [Europe PMC free article] [Abstract] [Google Scholar]
  • Wichmann I, Garcia-Lozano JR, Respaldiza N, Gonzalez-Escribano MF, Nuñez-Roldan A. Autoantibodies to transcriptional regulation proteins DEK and ALY in a patient with systemic lupus erythematosus. Hum Immunol. 1999 Jan;60(1):57–62. [Abstract] [Google Scholar]
  • Wilm M, Shevchenko A, Houthaeve T, Breit S, Schweigerer L, Fotsis T, Mann M. Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass spectrometry. Nature. 1996 Feb 1;379(6564):466–469. [Abstract] [Google Scholar]
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