Nuclear Export Receptors: From Importin to Exportin

Ullman, Katharine S.; Powers, Maureen A.; Forbes, Douglass J.

doi:10.1016/s0092-8674(00)80361-x

Cited by 252 publications

(192 citation statements)

References 21 publications

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“…Finally, the presence of the N G , N G -dimethylarginine could help determine the localization of the modified protein (Pintucci et al 1996) as demonstrated here. For instance, it could be mediating interactions of hnRNPs with the nuclear export machinery (Ullman et al 1997).…”

Section: Protein Methylation and Nuclear Export Genes And Development 685mentioning

confidence: 99%

Arginine methylation facilitates the nuclear export of hnRNP proteins

Shen

Henry²,

Weiss³

et al. 1998

Genes & Development

266

268

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Eukaryotic mRNA processing and export is mediated by various heterogeneous nuclear ribonucleoproteins (hnRNPs). Many of these hnRNPs are methylated on arginine residues. In the yeast, Saccharomyces cerevisiae, the predominant enzyme responsible for arginine methylation is Hmt1p. Hmt1p methylates both Npl3p and Hrp1p, which are shuttling hnRNPs involved in mRNA processing and export. Here, we employ an in vivo nuclear export assay to show that arginine methylation is important for the nuclear export of these hnRNPs. Both Npl3p and Hrp1p fail to exit the nucleus in cells lacking Hmt1p, and overexpression of Hmt1p enhances Npl3p export. The export of a novel hnRNP-like protein, Hrb1p, which does not bind poly(A) + RNA, however, is not affected by the lack of methylation. Furthermore, we find a genetic relationship between Hmt1p and cap-binding protein 80 (CBP80). Together, these findings establish that one biological role for arginine methylation is in facilitating the export of certain hnRNPs out of the nucleus. While in the nucleus, mRNA precursors, referred to as pre-mRNAs or heterogeneous nuclear RNAs (hnRNAs), undergo a series of processing events before traveling to the cytoplasm. These maturation events include capping at the 5Ј end, splicing, and 3Ј-end cleavage followed by polyadenylation. From the time they leave the transcription complex, hnRNAs are associated with proteins, some of which have been proposed to be mediators of RNA export (for review, see Lee and Silver 1997). The set of proteins that bind hnRNAs, with the exception of small nuclear RNPs, are referred to as heterogeneous nuclear ribonucleoproteins (hnRNPs).Among the most abundant proteins in the nucleus (Kiledjian et al. 1994), there are over 20 mammalian hnRNPs, proposed to function in nearly every step of mRNA maturation including export (Piñ ol-Roma 1997). One of the best-studied hnRNPs, hnRNP A1, travels back and forth between the nucleus and the cytoplasm in a process termed nucleocytoplasmic shuttling (Piñ olRoma and Dreyfuss 1992). In addition, an hnRNP A1-like protein in the insect Chironomus tentans can be seen by immunoelectron microscopy to be associated with pre-mRNA traveling through the nuclear pore to the cytoplasm (Visa et al. 1996a).The discovery of a nuclear export signal (NES) in some hnRNPs has suggested further that these hnRNPs could play an active role in RNA export. A 38-amino-acid sequence within hnRNP A1 termed M9 has been found to be necessary and sufficient for export of the protein to the cytoplasm (Michael et al. 1995). Microinjection experiments have shown that saturating amounts of the M9 domain block mRNA export in Xenopus oocytes . A model for mRNA export has been proposed in which the export signals on the shuttling hnRNPs are directly responsible for the translocation of bound mRNAs into the cytoplasm (Fischer et al. 1996;Nigg 1997). This model is best supported by studies of the HIV Rev protein. Through its leucine-rich NES, Rev facilitates the nuclear export of partially spliced and unspliced viral RNA...

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Section: Protein Methylation and Nuclear Export Genes And Development 685mentioning

confidence: 99%

Arginine methylation facilitates the nuclear export of hnRNP proteins

Shen

Henry²,

Weiss³

et al. 1998

Genes & Development

266

268

View full text Add to dashboard Cite

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“…Because Ran GAP is localized in the cytoplasm and the Ran guanine nucleotide exchange factor (GEF) RCC1 is located in the nucleus, a model has been proposed whereby RanGTP in the nucleus stimulates the formation of Crm1/NES complexes leading to nuclear export. Upon translocation into the cytoplasm, Crm1/ NES complexes are dissociated in the presence of RanGDP (for review, see Ullman et al 1997). This has led to the suggestion that ERK is retained in the cytoplasm by association with its activator, MEK, and that dissociation from MEK leads to its nuclear accumulation.…”

Section: How Does the Mapk Go Nuclear?mentioning

confidence: 99%

SAPKs and transcription factors do the nucleocytoplasmic tango: Figure 1.

Wilkinson¹,

Millar²

1998

Genes Dev.

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“…The poly(A) tail serves different purposes for mRNAs on their way to being translated into protein+ Polyadenylation is thought to be necessary for efficient export of mRNA from the nucleus (Ullman et al+, 1997;Hilleren et al+, 2001) and plays a role in the maintenance of mRNA stability in the cytoplasm (Decker & Parker, 1993;Brown & Sachs, 1998)+ Moreover, efficient mRNA translation also requires a poly(A) tail (Gallie, 1991;Iizuka et al+, 1994;+ Lack of a poly(A) tail can, therefore, result in unstable poorly translated mRNA and reduced amounts of gene product+…”

Section: Introductionmentioning

confidence: 99%

Replacement of the yeast TRP4 3??? untranslated region by a hammerhead ribozyme results in a stable and efficiently exported mRNA that lacks a poly(A) tail

Düvel

Valerius

Mangus

et al. 2002

RNA

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The mRNA poly(A) tail serves different purposes, including the facilitation of nuclear export, mRNA stabilization, efficient translation, and, finally, specific degradation. The posttranscriptional addition of a poly(A) tail depends on sequence motifs in the 39 untranslated region (39 UTR) of the mRNA and a complex trans-acting protein machinery. In this study, we have replaced the 39 UTR of the yeast TRP4 gene with sequences encoding a hammerhead ribozyme that efficiently cleaves itself in vivo. Expression of the TRP4-ribozyme allele resulted in the accumulation of a nonpolyadenylated mRNA. Cells expressing the TRP4-ribozyme mRNA showed a reduced growth rate due to a reduction in Trp4p enzyme activity. The reduction in enzyme activity was not caused by inefficient mRNA export from the nucleus or mRNA destabilization. Rather, analyses of mRNA association with polyribosomes indicate that translation of the ribozyme-containing mRNA is impaired. This translational defect allows sufficient synthesis of Trp4p to support growth of trp4 cells, but is, nevertheless, of such magnitude as to activate the general control network of amino acid biosynthesis.

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Nuclear Export Receptors: From Importin to Exportin

Cited by 252 publications

References 21 publications

Arginine methylation facilitates the nuclear export of hnRNP proteins

Arginine methylation facilitates the nuclear export of hnRNP proteins

SAPKs and transcription factors do the nucleocytoplasmic tango: Figure 1.

Replacement of the yeast TRP4 3??? untranslated region by a hammerhead ribozyme results in a stable and efficiently exported mRNA that lacks a poly(A) tail

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