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PMID: 9632798 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Functional conservation of the transportin nuclear import pathway in divergent organisms.

Molecular and cellular biology ·Vol. 18 ·No. 7 ·1998-07-00 ·Pages 4141-8

Siomi MC, Fromont M, Rain JC, Wan L, Wang F, Legrain P, Dreyfuss G

Abstract

Human transportin1 (hTRN1) is the nuclear import receptor for a group of pre-mRNA/mRNA-binding proteins (heterogeneous nuclear ribonucleoproteins [hnRNP]) represented by hnRNP A1, which shuttle continuously between the nucleus and the cytoplasm. hTRN1 interacts with the M9 region of hnRNP A1, a 38-amino-acid domain rich in Gly, Ser, and Asn, and mediates the nuclear import of M9-bearing proteins in vitro. Saccharomyces cerevisiae transportin (yTRN; also known as YBR017c or Kap104p) has been identified and cloned. To understanding the nuclear import mediated by yTRN, we searched with a yeast two-hybrid system for proteins that interact with it. In an exhaustive screen of the S. cerevisiae genome, the most frequently selected open reading frame was the nuclear mRNA-binding protein, Nab2p. We delineated a ca.-50-amino-acid region in Nab2p, termed NAB35, which specifically binds yTRN and is similar to the M9 motif. NAB35 also interacts with hTRN1 and functions as a nuclear localization signal in mammalian cells. Interestingly, yTRN can also mediate the import of NAB35-bearing proteins into mammalian nuclei in vitro. We also report on additional substrates for TRN as well as sequences of Drosophila melanogaster, Xenopus laevis, and Schizosaccharomyces pombe TRNs. Together, these findings demonstrate that both the M9 signal and the nuclear import machinery utilized by the transportin pathway are conserved in evolution.

MeSH Terms
Amino Acid Sequence Animals Biological Transport COS Cells Cell Nucleus/metabolism Conserved Sequence Drosophila melanogaster Fungal Proteins/metabolism Heterogeneous Nuclear Ribonucleoprotein A1 Heterogeneous-Nuclear Ribonucleoprotein Group A-B Heterogeneous-Nuclear Ribonucleoproteins Humans Karyopherins Molecular Sequence Data Nuclear Localization Signals Nuclear Proteins/metabolism Nucleocytoplasmic Transport Proteins RNA-Binding Proteins/metabolism Receptors, Cytoplasmic and Nuclear/metabolism Recombinant Fusion Proteins/metabolism Ribonucleoproteins/metabolism Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins Schizosaccharomyces Sequence Homology, Amino Acid Xenopus laevis
Chemicals
Fungal Proteins Heterogeneous Nuclear Ribonucleoprotein A1 Heterogeneous-Nuclear Ribonucleoprotein Group A-B Heterogeneous-Nuclear Ribonucleoproteins Karyopherins NAB2 protein, S cerevisiae Nuclear Localization Signals Nuclear Proteins Nucleocytoplasmic Transport Proteins RNA-Binding Proteins Receptors, Cytoplasmic and Nuclear Recombinant Fusion Proteins Ribonucleoproteins Saccharomyces cerevisiae Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Siomi M C
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
Fromont M
Rain J C
Wan L
Wang F
Legrain P
Dreyfuss G
References (45)
45 references, click to expand
  1. Primary structure of human nuclear ribonucleoprotein particle C proteins: conservation of sequence and domain structures in heterogeneous nuclear RNA, mRNA, and pre-rRNA-binding proteins.
    Mol Cell Biol. 1987 May;7(5):1731-9 PMID: 3110598
  2. Identification and functional characterization of a novel nuclear localization signal present in the yeast Nab2 poly(A)+ RNA binding protein.
    Mol Cell Biol. 1998 Mar;18(3):1449-58 PMID: 9488461
  3. Classification and purification of proteins of heterogeneous nuclear ribonucleoprotein particles by RNA-binding specificities.
    Mol Cell Biol. 1988 May;8(5):2237-41 PMID: 3386636
  4. RNA binding specificity of hnRNP proteins: a subset bind to the 3' end of introns.
    EMBO J. 1988 Nov;7(11):3519-29 PMID: 3208740
  5. Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors.
    J Cell Biol. 1990 Sep;111(3):807-16 PMID: 2391365
  6. Transcription-dependent and transcription-independent nuclear transport of hnRNP proteins.
    Science. 1991 Jul 19;253(5017):312-4 PMID: 1857966
  7. Characterization of the major hnRNP proteins from Drosophila melanogaster.
    J Cell Biol. 1992 Jan;116(2):257-69 PMID: 1730754
  8. Regulation of alternative pre-mRNA splicing by hnRNP A1 and splicing factor SF2.
    Cell. 1992 Jan 24;68(2):365-75 PMID: 1531115
  9. Nuclear targeting sequences--a consensus?
    Trends Biochem Sci. 1991 Dec;16(12):478-81 PMID: 1664152
  10. Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm.
    Nature. 1992 Feb 20;355(6362):730-2 PMID: 1371331
  11. Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box.
    EMBO J. 1992 Jul;11(7):2655-64 PMID: 1628625
  12. General splicing factors SF2 and SC35 have equivalent activities in vitro, and both affect alternative 5' and 3' splice site selection.
    Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11224-8 PMID: 1454802
  13. NAB2: a yeast nuclear polyadenylated RNA-binding protein essential for cell viability.
    Mol Cell Biol. 1993 May;13(5):2730-41 PMID: 8474438
  14. Mammalian Ras interacts directly with the serine/threonine kinase Raf.
    Cell. 1993 Jul 16;74(1):205-14 PMID: 8334704
  15. hnRNP proteins and the biogenesis of mRNA.
    Annu Rev Biochem. 1993;62:289-321 PMID: 8352591
  16. RNA binding specificity of hnRNP A1: significance of hnRNP A1 high-affinity binding sites in pre-mRNA splicing.
    EMBO J. 1994 Mar 1;13(5):1197-204 PMID: 7510636
  17. The hnRNP F protein: unique primary structure, nucleic acid-binding properties, and subcellular localization.
    Nucleic Acids Res. 1994 Mar 25;22(6):1059-67 PMID: 7512260
  18. The A1 and A1B proteins of heterogeneous nuclear ribonucleoparticles modulate 5' splice site selection in vivo.
    Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6924-8 PMID: 8041722
  19. Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors.
    Science. 1994 Sep 16;265(5179):1706-9 PMID: 8085156
  20. A nuclear localization domain in the hnRNP A1 protein.
    J Cell Biol. 1995 May;129(3):551-60 PMID: 7730395
  21. Identification of hSRP1 alpha as a functional receptor for nuclear localization sequences.
    Science. 1995 May 19;268(5213):1049-53 PMID: 7754385
  22. Nucleo-cytoplasmic distribution of human hnRNP proteins: a search for the targeting domains in hnRNP A1.
    J Cell Sci. 1995 Feb;108 ( Pt 2):545-55 PMID: 7769000
  23. The UUAG-specific RNA binding protein, heterogeneous nuclear ribonucleoprotein D0. Common modular structure and binding properties of the 2xRBD-Gly family.
    J Biol Chem. 1995 Sep 22;270(38):22167-75 PMID: 7673195
  24. A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway.
    Cell. 1995 Nov 3;83(3):415-22 PMID: 8521471
  25. A pre-mRNA-binding protein accompanies the RNA from the gene through the nuclear pores and into polysomes.
    Cell. 1996 Jan 26;84(2):253-64 PMID: 8565071
  26. Nucleocytoplasmic transport.
    Science. 1996 Mar 15;271(5255):1513-8 PMID: 8599106
  27. An improved method for polymerase chain reaction using whole yeast cells.
    Anal Biochem. 1996 May 15;237(1):145-6 PMID: 8660550
  28. Toward the molecular dissection of protein import into nuclei.
    Curr Opin Cell Biol. 1996 Jun;8(3):397-406 PMID: 8743893
  29. Potential RNA binding proteins in Saccharomyces cerevisiae identified as suppressors of temperature-sensitive mutations in NPL3.
    Genetics. 1996 Jan;142(1):103-15 PMID: 8770588
  30. A novel receptor-mediated nuclear protein import pathway.
    Cell. 1996 Sep 20;86(6):985-94 PMID: 8808633
  31. Signal sequences that target nuclear import and nuclear export of pre-mRNA-binding proteins.
    Cold Spring Harb Symp Quant Biol. 1995;60:663-8 PMID: 8824440
  32. The hnRNP C proteins contain a nuclear retention sequence that can override nuclear export signals.
    J Cell Biol. 1996 Sep;134(6):1365-73 PMID: 8830767
  33. Kap104p: a karyopherin involved in the nuclear transport of messenger RNA binding proteins.
    Science. 1996 Oct 25;274(5287):624-7 PMID: 8849456
  34. Transportin: nuclear transport receptor of a novel nuclear protein import pathway.
    Exp Cell Res. 1996 Dec 15;229(2):261-6 PMID: 8986607
  35. A role for the M9 transport signal of hnRNP A1 in mRNA nuclear export.
    J Cell Biol. 1997 Apr 7;137(1):27-35 PMID: 9105034
  36. Karyopherin beta2 mediates nuclear import of a mRNA binding protein.
    Proc Natl Acad Sci U S A. 1997 May 13;94(10):5055-60 PMID: 9144189
  37. Functional domains in nuclear import factor p97 for binding the nuclear localization sequence receptor and the nuclear pore.
    Mol Biol Cell. 1997 Jun;8(6):945-56 PMID: 9201707
  38. Nuclear import of hnRNP A1 is mediated by a novel cellular cofactor related to karyopherin-beta.
    J Cell Sci. 1997 Jun;110 ( Pt 11):1325-31 PMID: 9202393
  39. Toward a functional analysis of the yeast genome through exhaustive two-hybrid screens.
    Nat Genet. 1997 Jul;16(3):277-82 PMID: 9207794
  40. A novel class of RanGTP binding proteins.
    J Cell Biol. 1997 Jul 14;138(1):65-80 PMID: 9214382
  41. Transportin-mediated nuclear import of heterogeneous nuclear RNP proteins.
    J Cell Biol. 1997 Sep 22;138(6):1181-92 PMID: 9298975
  42. The asymmetric distribution of the constituents of the Ran system is essential for transport into and out of the nucleus.
    EMBO J. 1997 Nov 3;16(21):6535-47 PMID: 9351834
  43. RanBP1 is crucial for the release of RanGTP from importin beta-related nuclear transport factors.
    FEBS Lett. 1997 Dec 15;419(2-3):249-54 PMID: 9428644
  44. Import and export of the nuclear protein import receptor transportin by a mechanism independent of GTP hydrolysis.
    Curr Biol. 1998 Jan 15;8(2):89-95 PMID: 9427645
  45. Immunopurification of heterogeneous nuclear ribonucleoprotein particles reveals an assortment of RNA-binding proteins.
    Genes Dev. 1988 Feb;2(2):215-27 PMID: 3129338
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.7.4141
Published
1998-07-00
Pages
4141-8
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC108998
Subset
IM
Databases
GENBANK
AF059613, AF059614
External Links
PubMed source DOI: 10.1128/MCB.18.7.4141 PMC Full Text View journal details
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