Home LiteratureArticle Details
PMID: 18724935 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The mRNA export factor Gle1 and inositol hexakisphosphate regulate distinct stages of translation.

Cell ·Vol. 134 ·No. 4 ·2008-08-22 ·Pages 624-33

Bolger TA, Folkmann AW, Tran EJ, Wente SR

Abstract

Gene expression requires proper messenger RNA (mRNA) export and translation. However, the functional links between these consecutive steps have not been fully defined. Gle1 is an essential, conserved mRNA export factor whose export function is dependent on the small molecule inositol hexakisphosphate (IP(6)). Here, we show that both Gle1 and IP(6) are required for efficient translation termination in Saccharomyces cerevisiae and that Gle1 interacts with termination factors. In addition, Gle1 has a conserved physical association with the initiation factor eIF3, and gle1 mutants display genetic interactions with the eIF3 mutant nip1-1. Strikingly, gle1 mutants have defects in initiation, whereas strains lacking IP(6) do not. We propose that Gle1 functions together with IP(6) and the DEAD-box protein Dbp5 to regulate termination. However, Gle1 also independently mediates initiation. Thus, Gle1 is uniquely positioned to coordinate the mRNA export and translation mechanisms. These results directly impact models for perturbation of Gle1 function in pathophysiology.

MeSH Terms
Carrier Proteins/metabolism DEAD-box RNA Helicases/metabolism Eukaryotic Initiation Factor-3/metabolism Nuclear Pore Complex Proteins Nucleocytoplasmic Transport Proteins/metabolism Peptide Termination Factors/metabolism Phytic Acid/metabolism Protein Biosynthesis Protein Isoforms/metabolism RNA, Messenger/metabolism Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/metabolism
Chemicals
Carrier Proteins Eukaryotic Initiation Factor-3 GLE1 protein, S cerevisiae Nuclear Pore Complex Proteins Nucleocytoplasmic Transport Proteins Peptide Termination Factors Protein Isoforms RNA, Messenger SUP45 protein, S cerevisiae Saccharomyces cerevisiae Proteins Phytic Acid DBP5 protein, S cerevisiae DEAD-box RNA Helicases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Bolger Timothy A
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, U-3209 MRBIII, 465 21st Avenue South, Nashville, TN 37232-8240, USA.
Folkmann Andrew W
Tran Elizabeth J
Wente Susan R
References (45)
45 references, click to expand
  1. Exporting RNA from the nucleus to the cytoplasm.
    Nat Rev Mol Cell Biol. 2007 Oct;8(10):761-73 PMID: 17786152
  2. Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export.
    Nat Cell Biol. 2006 Jul;8(7):668-76 PMID: 16783364
  3. Recycling of eukaryotic posttermination ribosomal complexes.
    Cell. 2007 Oct 19;131(2):286-99 PMID: 17956730
  4. Mex67p, a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores.
    EMBO J. 1997 Jun 2;16(11):3256-71 PMID: 9214641
  5. A conditional allele of the novel repeat-containing yeast nucleoporin RAT7/NUP159 causes both rapid cessation of mRNA export and reversible clustering of nuclear pore complexes.
    J Cell Biol. 1995 May;129(4):939-55 PMID: 7744966
  6. A temperature-sensitive NUP116 null mutant forms a nuclear envelope seal over the yeast nuclear pore complex thereby blocking nucleocytoplasmic traffic.
    J Cell Biol. 1993 Oct;123(2):275-84 PMID: 7691829
  7. A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export.
    Science. 1999 Jul 2;285(5424):96-100 PMID: 10390371
  8. Dbp5p/Rat8p is a yeast nuclear pore-associated DEAD-box protein essential for RNA export.
    EMBO J. 1998 May 1;17(9):2663-76 PMID: 9564048
  9. The DEAD-box protein Dbp5 controls mRNA export by triggering specific RNA:protein remodeling events.
    Mol Cell. 2007 Dec 14;28(5):850-9 PMID: 18082609
  10. Rat8p/Dbp5p is a shuttling transport factor that interacts with Rat7p/Nup159p and Gle1p and suppresses the mRNA export defect of xpo1-1 cells.
    EMBO J. 1999 Oct 15;18(20):5778-88 PMID: 10523319
  11. Eukaryotic translation initiation factor 4E regulates expression of cyclin D1 at transcriptional and post-transcriptional levels.
    J Biol Chem. 1995 Sep 8;270(36):21176-80 PMID: 7673150
  12. Isolation and characterization of omnipotent suppressors in the yeast Saccharomyces cerevisiae.
    Genetics. 1990 Mar;124(3):515-22 PMID: 2179051
  13. A conserved family of enzymes that phosphorylate inositol hexakisphosphate.
    Science. 2007 Apr 6;316(5821):106-9 PMID: 17412958
  14. Tap and NXT promote translation of unspliced mRNA.
    Genes Dev. 2003 Dec 15;17(24):3075-86 PMID: 14701875
  15. eIF4E is a central node of an RNA regulon that governs cellular proliferation.
    J Cell Biol. 2006 Nov 6;175(3):415-26 PMID: 17074885
  16. From birth to death: the complex lives of eukaryotic mRNAs.
    Science. 2005 Sep 2;309(5740):1514-8 PMID: 16141059
  17. The mRNA export factor human Gle1 interacts with the nuclear pore complex protein Nup155.
    Mol Cell Proteomics. 2004 Feb;3(2):145-55 PMID: 14645504
  18. 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):1921-37 PMID: 8970155
  19. Intracellular trafficking of RNA in neurons.
    Traffic. 2006 Dec;7(12):1581-9 PMID: 17054760
  20. Functions of eIF3 downstream of 48S assembly impact AUG recognition and GCN4 translational control.
    EMBO J. 2004 Mar 10;23(5):1166-77 PMID: 14976554
  21. Global analysis of protein expression in yeast.
    Nature. 2003 Oct 16;425(6959):737-41 PMID: 14562106
  22. Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export.
    Nat Cell Biol. 2006 Jul;8(7):711-6 PMID: 16783363
  23. The eukaryotic polypeptide chain releasing factor (eRF3/GSPT) carrying the translation termination signal to the 3'-Poly(A) tail of mRNA. Direct association of erf3/GSPT with polyadenylate-binding protein.
    J Biol Chem. 1999 Jun 11;274(24):16677-80 PMID: 10358005
  24. Translational regulation of GCN4 and the general amino acid control of yeast.
    Annu Rev Microbiol. 2005;59:407-50 PMID: 16153175
  25. Versatile vectors to study recoding: conservation of rules between yeast and mammalian cells.
    Nucleic Acids Res. 1995 May 11;23(9):1557-60 PMID: 7784210
  26. Yeast shuttling SR proteins Npl3p, Gbp2p, and Hrb1p are part of the translating mRNPs, and Npl3p can function as a translational repressor.
    Mol Cell Biol. 2004 Dec;24(23):10479-91 PMID: 15542855
  27. The product of the Saccharomyces cerevisiae RSS1 gene, identified as a high-copy suppressor of the rat7-1 temperature-sensitive allele of the RAT7/NUP159 nucleoporin, is required for efficient mRNA export.
    Mol Biol Cell. 1996 Oct;7(10):1601-21 PMID: 8898365
  28. An essential role for hGle1 nucleocytoplasmic shuttling in mRNA export.
    J Cell Biol. 2003 Mar 31;160(7):1029-40 PMID: 12668658
  29. 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):6779-84 PMID: 9618489
  30. The molecular mechanics of eukaryotic translation.
    Annu Rev Biochem. 2004;73:657-704 PMID: 15189156
  31. Factors affecting nuclear export of the 60S ribosomal subunit in vivo.
    Mol Biol Cell. 2000 Nov;11(11):3777-89 PMID: 11071906
  32. A subcomplex of three eIF3 subunits binds eIF1 and eIF5 and stimulates ribosome binding of mRNA and tRNA(i)Met.
    EMBO J. 2001 Jun 1;20(11):2954-65 PMID: 11387228
  33. Interaction between the shuttling mRNA export factor Gle1 and the nucleoporin hCG1: a conserved mechanism in the export of Hsp70 mRNA.
    Mol Biol Cell. 2005 Sep;16(9):4304-15 PMID: 16000379
  34. TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus.
    Mol Cell. 1998 Apr;1(5):649-59 PMID: 9660949
  35. An RNA-export mediator with an essential nuclear export signal.
    Nature. 1996 Sep 26;383(6598):357-60 PMID: 8848052
  36. Cross-talks between transcription and post-transcriptional events within a 'mRNA factory'.
    J Biochem. 2007 Jul;142(1):11-5 PMID: 17567655
  37. Domain analysis of the Saccharomyces cerevisiae heterogeneous nuclear ribonucleoprotein, Nab2p. Dissecting the requirements for Nab2p-facilitated poly(A) RNA export.
    J Biol Chem. 2003 Feb 28;278(9):6731-40 PMID: 12496292
  38. The DEAD-box RNA helicase Dbp5 functions in translation termination.
    Science. 2007 Feb 2;315(5812):646-9 PMID: 17272721
  39. eIF3: a versatile scaffold for translation initiation complexes.
    Trends Biochem Sci. 2006 Oct;31(10):553-62 PMID: 16920360
  40. Association of RAP1 binding sites with stringent control of ribosomal protein gene transcription in Saccharomyces cerevisiae.
    Mol Cell Biol. 1991 May;11(5):2723-35 PMID: 2017175
  41. 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):4332-47 PMID: 10428971
  42. Nip1p associates with 40 S ribosomes and the Prt1p subunit of eukaryotic initiation factor 3 and is required for efficient translation initiation.
    J Biol Chem. 1998 Sep 4;273(36):23485-94 PMID: 9722586
  43. The Mex67p-mediated nuclear mRNA export pathway is conserved from yeast to human.
    EMBO J. 1999 May 4;18(9):2593-609 PMID: 10228171
  44. Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases.
    Curr Biol. 1999 Nov 18;9(22):1323-6 PMID: 10574768
  45. Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease.
    Nat Genet. 2008 Feb;40(2):155-7 PMID: 18204449
Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2008.06.027
Published
2008-08-22
Pages
624-33
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2601711
Subset
IM
Grants
NCI NIH HHS · T32 CA009582-21 · United States
NCI NIH HHS · T32 CA119925 · United States
NIGMS NIH HHS · R01 GM051219-09 · United States
NCI NIH HHS · 1T32-CA009582 · United States
NIGMS NIH HHS · 1F32-GM082065 · United States
NIGMS NIH HHS · R37 GM051219 · United States
NIGMS NIH HHS · F32 GM082065 · United States
NCI NIH HHS · T32 CA009582 · United States
NIGMS NIH HHS · F32 GM082065-02 · United States
NIGMS NIH HHS · R01-GM51219 · United States
NIGMS NIH HHS · R01 GM051219 · United States
Corrections
CommentIn
PMID: 18724928
External Links
PubMed source DOI: 10.1016/j.cell.2008.06.027 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2