A Conserved mRNA Export Machinery Coupled to pre-mRNA Splicing

Recent advances have led to a new understanding of how mRNAs are exported from the nucleus to the cytoplasm. This process requires a heterodimeric mRNA export receptor that is part of an elaborate machinery conserved from yeast to humans. Export of mRNAs is coupled to upstream steps in gene expression, such as pre-mRNA splicing, and to downstream events, including nonsense-mediated decay.

[1]  M. Stewart,et al.  The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2). , 1997, Journal of molecular biology.

[2]  Ed Hurt,et al.  Binding of the Mex67p/Mtr2p Heterodimer to Fxfg, Glfg, and Fg Repeat Nucleoporins Is Essential for Nuclear mRNA Export , 2000, The Journal of cell biology.

[3]  L. Maquat Nuclear mRNA export. , 1991, Current opinion in cell biology.

[4]  A. Podtelejnikov,et al.  The Mex67p‐mediated nuclear mRNA export pathway is conserved from yeast to human , 1999, The EMBO journal.

[5]  D. Bentley,et al.  Coupling RNA polymerase II transcription with pre-mRNA processing. , 1999, Current opinion in cell biology.

[6]  M. Rosbash,et al.  A block to mRNA nuclear export in S. cerevisiae leads to hyperadenylation of transcripts that accumulate at the site of transcription. , 2001, Molecular cell.

[7]  J. Yong,et al.  The Y14 protein communicates to the cytoplasm the position of exon–exon junctions , 2001, The EMBO journal.

[8]  Helen M. Kent,et al.  The 1.6 Å Resolution Crystal Structure of Nuclear Transport Factor 2 (NTF2) , 1996 .

[9]  R. Reed,et al.  A Ran-independent pathway for export of spliced mRNA , 2000, Nature Cell Biology.

[10]  R. Reed,et al.  Splicing is required for rapid and efficient mRNA export in metazoans. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[11]  C. Cole,et al.  Rat8p/Dbp5p is a shuttling transport factor that interacts with Rat7p/Nup159p and Gle1p and suppresses the mRNA export defect of xpo1‐1 cells , 1999, The EMBO journal.

[12]  E. Conti,et al.  Nucleocytoplasmic transport enters the atomic age. , 2001, Current opinion in cell biology.

[13]  Marco M. Kessler,et al.  Hrp1, a sequence-specific RNA-binding protein that shuttles between the nucleus and the cytoplasm, is required for mRNA 3'-end formation in yeast. , 1997, Genes & development.

[14]  P. Bork,et al.  REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export. , 2000, RNA.

[15]  A. Burlingame,et al.  Proteomic Analysis of Nucleoporin Interacting Proteins* , 2001, The Journal of Biological Chemistry.

[16]  B. Séraphin,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 , 1999, The EMBO journal.

[17]  G. Blobel,et al.  Two yeast nuclear pore complex proteins involved in mRNA export form a cytoplasmically oriented subcomplex. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[18]  P. Silver,et al.  7The Yeast mRNA-binding Protein Npl3p Interacts with the Cap-binding Complex* , 2000, The Journal of Biological Chemistry.

[19]  L. Gerace,et al.  In Vitro Analysis of Nuclear Transport Mediated by the C-terminal Shuttle Domain of Tap* , 2001, The Journal of Biological Chemistry.

[20]  R. Lührmann,et al.  Mex67p, a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores , 1997, The EMBO journal.

[21]  R Grosschedl,et al.  ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function. , 1997, Genes & development.

[22]  T. Littlewood,et al.  Molecular mechanism of translocation through nuclear pore complexes during nuclear protein import , 2001, FEBS letters.

[23]  B. Chait,et al.  The Yeast Nuclear Pore Complex , 2000, The Journal of cell biology.

[24]  B. Séraphin,et al.  Dbp 5 , a DEAD-box protein required for mRNA export , is recruited to the cytoplasmic fibrils of nuclear pore complex via a conserved interaction with CAN / Nup 159 p , 1999 .

[25]  H. Le Hir,et al.  The exon–exon junction complex provides a binding platform for factors involved in mRNA export and nonsense‐mediated mRNA decay , 2001, The EMBO journal.

[26]  S. Wente,et al.  An RNA-export mediator with an essential nuclear export signal , 1996, Nature.

[27]  S. Chen,et al.  Nuclear mRNA accumulation causes nucleolar fragmentation in yeast mtr2 mutant. , 1994, Molecular biology of the cell.

[28]  C. Guthrie,et al.  Deletion of MUD2, the yeast homolog of U2AF65, can bypass the requirement for sub2, an essential spliceosomal ATPase. , 2001, Genes & development.

[29]  J. L. Watkins,et al.  The human homologue of Saccharomyces cerevisiae Gle1p is required for poly(A)+ RNA export. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[30]  B. Daneholt A Look at Messenger RNP Moving through the Nuclear Pore , 1997, Cell.

[31]  U. Kutay,et al.  Transport between the cell nucleus and the cytoplasm. , 1999, Annual review of cell and developmental biology.

[32]  J. Steitz,et al.  Human Upf Proteins Target an mRNA for Nonsense-Mediated Decay When Bound Downstream of a Termination Codon , 2000, Cell.

[33]  J. Steitz,et al.  Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA. , 2001, Molecular cell.

[34]  J. Yong,et al.  Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm. , 2000, Molecular cell.

[35]  Xiang-Dong Fu,et al.  Conserved Sr Protein Kinase Functions in Nuclear Import and Its Action Is Counteracted by Arginine Methylation in Saccharomyces cerevisiae , 2000, The Journal of cell biology.

[36]  G. Dreyfuss,et al.  YRA1, an essential Saccharomyces cerevisiae gene, encodes a novel nuclear protein with RNA annealing activity. , 1997, RNA.

[37]  P. Silver,et al.  Pre-mRNA processing factors are required for nuclear export. , 2000, RNA.

[38]  R. Parker,et al.  Defects in the mRNA export factors Rat7p, Gle1p, Mex67p, and Rat8p cause hyperadenylation during 3'-end formation of nascent transcripts. , 2001, RNA.

[39]  Helena Santos-Rosa,et al.  Nuclear mRNA Export Requires Complex Formation between Mex67p and Mtr2p at the Nuclear Pores , 1998, Molecular and Cellular Biology.

[40]  B. Graveley Sorting out the complexity of SR protein functions. , 2000, RNA.

[41]  Angela Bachi,et al.  PHAX, a Mediator of U snRNA Nuclear Export Whose Activity Is Regulated by Phosphorylation , 2000, Cell.

[42]  J. Steitz,et al.  Delineation of mRNA Export Pathways by the Use of Cell-Permeable Peptides , 2001, Science.

[43]  B. Fahrenkrog,et al.  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 Ymr255p , 1999, The EMBO journal.

[44]  B. Blencowe,et al.  REF proteins mediate the export of spliced and unspliced mRNAs from the nucleus. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[45]  M. Mann,et al.  Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly , 2001, Nature.

[46]  J. L. Watkins,et al.  GLE2, a Saccharomyces cerevisiae homologue of the Schizosaccharomyces pombe export factor RAE1, is required for nuclear pore complex structure and function. , 1996, Molecular biology of the cell.

[47]  J. R. Warner,et al.  Nascent Ribosomes , 2001, Cell.

[48]  K Strässer,et al.  Yra1p, a conserved nuclear RNA‐binding protein, interacts directly with Mex67p and is required for mRNA export , 2000, The EMBO journal.

[49]  T. Hope,et al.  Splicing-Independent Expression of the Herpes Simplex Virus Type 1 Thymidine Kinase Gene Is Mediated by Three cis-Acting RNA Subelements , 1998, Journal of Virology.

[50]  R. Reed,et al.  A new view of mRNA export: Separating the wheat from the chaff , 2001, Nature Cell Biology.

[51]  P. Majerus,et al.  Overexpression of the inositol phosphatase SopB in human 293 cells stimulates cellular chloride influx and inhibits nuclear mRNA export. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[52]  B. E. Black,et al.  NXT1 (p15) Is a Crucial Cellular Cofactor in TAP-Dependent Export of Intron-Containing RNA in Mammalian Cells , 2001, Molecular and Cellular Biology.

[53]  D. Page,et al.  Two closely related human nuclear export factors utilize entirely distinct export pathways. , 2001, Molecular cell.

[54]  J. Steitz,et al.  Communication of the Position of Exon-Exon Junctions to the mRNA Surveillance Machinery by the Protein RNPS1 , 2001, Science.

[55]  Stavroula Mili,et al.  Distinct RNP Complexes of Shuttling hnRNP Proteins with Pre-mRNA and mRNA: Candidate Intermediates in Formation and Export of mRNA , 2001, Molecular and Cellular Biology.

[56]  Richard Bayliss,et al.  Structural Basis for the Interaction between FxFG Nucleoporin Repeats and Importin-β in Nuclear Trafficking , 2000, Cell.

[57]  M. Rode,et al.  Overexpression of TAP/p15 Heterodimers Bypasses Nuclear Retention and Stimulates Nuclear mRNA Export* , 2001, The Journal of Biological Chemistry.

[58]  G. Blobel,et al.  mRNA binding protein mrnp 41 localizes to both nucleus and cytoplasm. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[59]  W. Tan,et al.  The mRNA export in Caenorhabditis elegans is mediated by Ce-NXF-1, an ortholog of human TAP/NXF and Saccharomyces cerevisiae Mex67p. , 2000, RNA.

[60]  T. Köcher,et al.  The DExH/D box protein HEL/UAP56 is essential for mRNA nuclear export in Drosophila , 2001, Current Biology.

[61]  D. Libri,et al.  Multiple roles for the yeast SUB2/yUAP56 gene in splicing. , 2001, Genes & development.

[62]  E. Hudson,et al.  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 , 1999, Molecular and Cellular Biology.

[63]  Daniel Zenklusen,et al.  The Yeast hnRNP-Like Proteins Yra1p and Yra2p Participate in mRNA Export through Interaction with Mex67p , 2001, Molecular and Cellular Biology.

[64]  Ed Hurt,et al.  Splicing factor Sub2p is required for nuclear mRNA export through its interaction with Yra1p , 2001, Nature.

[65]  J. Manley,et al.  RNA polymerase II and the integration of nuclear events. , 2000, Genes & development.

[66]  Yan Liu,et al.  Dbp5p, a cytosolic RNA helicase, is required for poly(A)+ RNA export , 1998, The EMBO journal.

[67]  E. Conti,et al.  Structural basis for the recognition of a nucleoporin FG repeat by the NTF2-like domain of the TAP/p15 mRNA nuclear export factor. , 2001, Molecular cell.

[68]  Michael Q. Zhang,et al.  Purification and characterization of human RNPS1: a general activator of pre‐mRNA splicing , 1999, The EMBO journal.

[69]  P. Silver,et al.  Messenger RNAs are recruited for nuclear export during transcription. , 2001, Genes & development.

[70]  M. Rosbash,et al.  The DECD box putative ATPase Sub2p is an early mRNA export factor , 2001, Current Biology.

[71]  E. Izaurralde,et al.  RNA Export , 1995, Cell.

[72]  E. Hurt,et al.  The protein Aly links pre-messenger-RNA splicing to nuclear export in metazoans , 2000, Nature.

[73]  I. Mattaj,et al.  Nucleocytoplasmic transport: the soluble phase. , 1998, Annual review of biochemistry.

[74]  B. Chait,et al.  The Yeast Nuclear Pore Complex: Composition, Architecture, and Transport Mechanism , 2000 .

[75]  H. Le Hir,et al.  The spliceosome deposits multiple proteins 20–24 nucleotides upstream of mRNA exon–exon junctions , 2000, The EMBO journal.

[76]  A. Krainer,et al.  A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm. , 1998, Genes & development.

[77]  M. Ruiz-Echevarría,et al.  Identifying the right stop: determining how the surveillance complex recognizes and degrades an aberrant mRNA , 1998, The EMBO journal.

[78]  G. Dreyfuss,et al.  Transport of Proteins and RNAs in and out of the Nucleus , 1999, Cell.

[79]  P. Chardon,et al.  The BAT1 gene in the MHC encodes an evolutionarily conserved putative nuclear RNA helicase of the DEAD family. , 1995, Genomics.

[80]  W. Gilbert,et al.  Phosphorylation by Sky1p promotes Npl3p shuttling and mRNA dissociation. , 2001, RNA.

[81]  M. Wilm,et al.  TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. , 1998, Molecular cell.

[82]  G. Dreyfuss,et al.  A Role for the M9 Transport Signal of hnRNP A1 in mRNA Nuclear Export , 1997, The Journal of cell biology.

[83]  C. Cole,et al.  Dbp5p/Rat8p is a yeast nuclear pore‐associated DEAD‐box protein essential for RNA export , 1998, The EMBO journal.

[84]  M. Green,et al.  A human nuclear-localized chaperone that regulates dimerization, DNA binding, and transcriptional activity of bZIP proteins. , 1999, Molecular cell.

[85]  J. Steitz,et al.  Protein Ligands to Hur Modulate Its Interaction with Target Mrnas in Vivo , 2000, The Journal of cell biology.

[86]  U. Kutay,et al.  The C-terminal domain of TAP interacts with the nuclear pore complex and promotes export of specific CTE-bearing RNA substrates. , 2000, RNA.

[87]  B. Cullen,et al.  The human Tap protein is a nuclear mRNA export factor that contains novel RNA-binding and nucleocytoplasmic transport sequences. , 1999, Genes & development.

[88]  A. Furger,et al.  Integrating mRNA Processing with Transcription , 2002, Cell.

[89]  G. Dreyfuss,et al.  Role of the Nonsense-Mediated Decay Factor hUpf3 in the Splicing-Dependent Exon-Exon Junction Complex , 2001, Science.

[90]  P. Silver,et al.  A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export. , 1996, Genes & development.

[91]  M. Suyama,et al.  TAP (NXF1) Belongs to a Multigene Family of Putative RNA Export Factors with a Conserved Modular Architecture , 2000, Molecular and Cellular Biology.

[92]  S. Vasu,et al.  Nuclear pores and nuclear assembly. , 2001, Current opinion in cell biology.

[93]  G. Blobel,et al.  Transport routes through the nuclear pore complex. , 1998, Current opinion in cell biology.

[94]  J. York,et al.  A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. , 1999, Science.

[95]  Julie A. Brown,et al.  A Mutation in the Schizosaccharomyces pombe rae1 Gene Causes Defects in Poly(A)+ RNA Export and in the Cytoskeleton (*) , 1995, The Journal of Biological Chemistry.

[96]  M. Green,et al.  Identification and characterization of yUAP/Sub2p, a yeast homolog of the essential human pre-mRNA splicing factor hUAP56. , 2001, Genes & development.

[97]  J. Valcárcel,et al.  U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction. , 1997, Genes & development.

[98]  J. Yoon,et al.  Mex67p of Schizosaccharomyces pombeInteracts with Rae1p in Mediating mRNA Export , 2000, Molecular and Cellular Biology.