A nuclear cap binding protein complex involved in pre-mRNA splicing

Izaurralde, Elisa; Lewis, Joe; McGuigan, C.; Jankowska, Marzena; Darżynkiewicz, Edward; Mattaj, Iain W.

doi:10.1016/0092-8674(94)90530-4

Cited by 484 publications

(515 citation statements)

References 53 publications

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“…Subcloning of complementing plasmids localized the minimal region required to a 4.2-kb ClaI DNA fragment. DNA sequence analysis and BLASTn searches revealed a single complete ORF that encodes the yeast homolog of the human cap-binding protein 80 (CBP80) (Izaurralde et al 1994).…”

Section: Synthetic Lethality With Hmt1mentioning

confidence: 99%

“…In strains containing a mutant allele of the gene encoding CBP80, HMT1 is required for viability. Cbp80p and another protein termed Cbp20p form the cap-binding protein complex (CBC) (Izaurralde et al 1994;Lewis et al 1996). Cbp80p and Cbp20p have been isolated in yeast by both genetic and biochemical approaches (Uemera and Jigami 1992;Colot et al 1996;Gorlich et al 1996).…”

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

confidence: 99%

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Arginine methylation facilitates the nuclear export of hnRNP proteins

Shen

Henry²,

Weiss³

et al. 1998

Genes & Development

263

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: Synthetic Lethality With Hmt1mentioning

confidence: 99%

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

263

268

View full text Add to dashboard Cite

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“…Interactions between different pre-mRNA processing machineries have been observed in vitro and in transfection experiments. The nuclear cap binding complex, CBC, stimulates excision of the most 5Ј-located intron in vitro (Ohno et al 1987;Inoue et al 1989;Izaurralde et al 1994) and has been shown to facilitate U1 snRNP binding to the cap-proximal 5Ј-splice site (Lewis et al 1996). It has also been shown that CBC enhances endonucleolytic cleavage at the polyadenylation site (Flaherty et al 1997).…”

mentioning

confidence: 99%

Transcriptional termination in the Balbiani ring 1 gene is closely coupled to 3′-end formation and excision of the 3′-terminal intron

Baurén

Беликов²,

Wieslander³

1998

Genes Dev.

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We have analyzed transcription termination, 3 -end formation, and excision of the 3 -terminal intron in vivo in the Balbiani ring 1 (BR1) gene and its pre-mRNA. We show that full-length RNA transcripts are evenly spaced on the gene from a position 300 bp upstream to a region 500-700 bp downstream of the polyadenylation sequence. Very few full-length transcripts and no short, cleaved, nascent transcripts could be observed downstream of this region. Pre-mRNA with 10-20 adenylate residues accumulates at the active gene and then rapidly leaves from the gene locus. Only polyadenylated pre-mRNAs could be detected in the nucleoplasm. Our results are consistent with the hypothesis that transcription termination occurs in a narrow region for the majority of transcripts, simultaneous with 3 -end formation. Excision of the 3 -terminal intron occurs before 3 -end formation in about 5% of the nascent transcripts. When transcription terminates, 3 cleavage takes place and 10-20 adenylate residues are added, the 3 -terminal intron is excised from additionally about 75% of the pre-mRNA at the gene locus. Our data support a close temporal and spatial coupling of transcription termination and the cleavage and initial polyadenylation of 3 -end formation. Excision of the 3 -terminal intron is highly stimulated as the cleavage/polyadenylation complex assembles and 3 -end formation is initiated.

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“…A nuclear cap-binding complex composed of two subunits, CBP20 and CBP80, facilitates spliceosome assembly (8). Interestingly, the same complex has been implicated in the cap-dependent export of U small nuclear RNA and mRNA (15,36).…”

mentioning

confidence: 99%

Cloning and Characterization of 4EHP, a Novel Mammalian eIF4E-related Cap-binding Protein

Rom

Kim

Gingras

et al. 1998

Journal of Biological Chemistry

131

155

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All eukaryotic mRNAs (except organellar) are capped at their 5 end. The cap structure (m 7 GpppN, where N is any nucleotide) is extremely important for the processing and translation of mRNA. Several cap-binding proteins that facilitate these processes have been characterized. Here we describe a novel human cytoplasmic protein that is 30% identical and 60% similar to the human translation initiation factor 4E (eIF4E). We demonstrate that this protein, named 4E Homologous Protein (4EHP), binds specifically to capped RNA in an ATP-and divalent ion-independent manner. The three-dimensional structure of 4EHP, as predicted by homology modeling, closely resembles that of eIF4E and site-directed mutagenesis analysis of 4EHP strongly suggests that it shares with eIF4E a common mechanism for cap binding. A putative function for 4EHP is discussed.

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A nuclear cap binding protein complex involved in pre-mRNA splicing

Cited by 484 publications

References 53 publications

Arginine methylation facilitates the nuclear export of hnRNP proteins

Arginine methylation facilitates the nuclear export of hnRNP proteins

Transcriptional termination in the Balbiani ring 1 gene is closely coupled to 3′-end formation and excision of the 3′-terminal intron

Cloning and Characterization of 4EHP, a Novel Mammalian eIF4E-related Cap-binding Protein

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