Nucleocytoplasmic Transport: Integrating mRNA Production and Turnover with Export through the Nuclear Pore

Dimaano, Christian; Ullman, Katharine S.

doi:10.1128/mcb.24.8.3069-3076.2004

Cited by 61 publications

(39 citation statements)

References 98 publications

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“…A direct interaction between the two proteins was confirmed by showing that 35 Slabeled, in vitro translated Fir1p (amino acids 173-876) bound GST-Sin1p fusion proteins derived from the N terminus of the protein, whereas GST alone did not bind (Fig. 2).…”

Section: Sin1p Binds Downstream Of Many Genes Just Upstream Of a Majormentioning

confidence: 74%

“…As details of the gene expression machinery are explored, it is becoming apparent that sometimes unexpected functional relationships exist between the different components (35)(36)(37)(38). Further research will be necessary to determine the details of how the mRNA processing machinery is recruited and activated.…”

Section: Discussionmentioning

confidence: 99%

“…Coupled transcription-translation of [ 35 S]methionine-labeled Fir1p peptides was accomplished by using the Promega TNT system. Plasmids encoding the GST͞ Sin1p fusions were described in ref.…”

mentioning

confidence: 99%

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Recruitment of mRNA cleavage/polyadenylation machinery by the yeast chromatin protein Sin1p/Spt2p

Hershkovits

Bangio²,

Cohen³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The yeast chromatin protein Sin1p͞Spt2p has long been studied, but the understanding of its function has remained elusive. The protein has sequence similarity to HMG1, specifically binds crossing DNA structures, and serves as a negative transcriptional regulator of a small family of genes that are activated by the SWI͞SNF chromatin-remodeling complex. Recently, it has been implicated in maintaining the integrity of chromatin during transcription elongation. Here we present experiments whose results indicate that Sin1p͞Spt2 is required for, and is directly involved in, the efficient recruitment of the mRNA cleavage͞polyadenylation complex. This conclusion is based on the following findings: Sin1p͞Spt2 frequently binds specifically downstream of many ORFs but almost always upstream of the first polyadenylation site. It directly interacts with Fir1p, a component of the cleavage͞polyadenylation complex. Disruption of Sin1p͞Spt2p results in foreshortened poly(A) tracts on mRNA. It is synthetically lethal with Cdc73p, which is involved in the recruitment of the complex. This report shows that a chromatin component is involved in 3 end processing of RNA. S in1p is a yeast chromatin nonhistone protein that has beenshown to function as a negative transcriptional regulator of several genes, including Suc2 (1), Ino1 (2), and SSA3 (3). Activity of the HO promoter, as measured from an HO promoter driving a lacZ gene (4), is also affected by Sin1. Sin1 (also known as spt2 in this context) mutants were identified as suppressors of Ty and insertions in the 5Ј noncoding region of the HIS4 gene (5). Because the negative regulation of these genes is overcome by the SW1͞SNF chromatin-remodeling complex (4, 6, 7) and the C-terminal domain of Sin1p interacts with Swi1p (8), it was suggested that a function of SIN1p is to somehow maintain chromatin compaction at specific loci in the chromatin. Peterson et al. (2) found a functional relationship between the C-terminal domain (CTD) of RNA polymerase II and Sin1p, but these data were not pursued further. Sequence analysis of Sin1p showed sequence similarity in two domains to HMG1 (6, 7), a known chromatin protein. Work from our laboratory showed that Sin1p can bind four-way junction and crossing DNA structures (9), supporting the idea that Sin1p binds DNA as it enters and exits the nucleosome.In the context of a global mapping project, Tong et al. (10) reported that there is a synthetic lethal interaction between sin1 and cdc73, a member of the PAF complex. The PAF complex, which accompanies RNA polymerase II during elongation, was shown to have an important function in 3Ј end formation and in polyadenylation (11-13). In addition, a functional interaction was demonstrated between Sin1p and Hpr1p, which is associated with the PAF complex (14).Most recently, evidence has been presented indicating that Sin1p͞Spt2p plays roles in transcription elongation, chromatin structure and genome stability (15). In that study, synthetic lethal interactions were reported between sin1 and paf1, and betwe...

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Section: Sin1p Binds Downstream Of Many Genes Just Upstream Of a Majormentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

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Recruitment of mRNA cleavage/polyadenylation machinery by the yeast chromatin protein Sin1p/Spt2p

Hershkovits

Bangio²,

Cohen³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Its encoded protein NXF1 is ubiquitously expressed in all tissue cells tested and is believed to be responsible for the nuclear export of bulk cellular mRNAs (for review, see ref. 27). Based on a recent report that Nxf1 mRNA can be alternatively spliced (28), we have chosen a primer pair that only amplifies the full-length NXF1-encoding mRNA in our qRT-PCR analysis to avoid possible complications in data interpretation.…”

Section: Discussionmentioning

confidence: 99%

“…After binding mRNPs, NXF1 interacts with nuclear pore components to facilitate export (for review, see ref. 27). A number of RNA-binding proteins have been identified as adaptor proteins for NXF1 (32; for review, see ref.…”

Section: Discussionmentioning

confidence: 99%

Fragile X mental retardation protein FMRP and the RNA export factor NXF2 associate with and destabilize Nxf1 mRNA in neuronal cells

Zhang

Wang

Huang

2007

Proc. Natl. Acad. Sci. U.S.A.

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Fragile X syndrome is caused by the inactivation of the X-linked FMR1 gene, leading to the loss of its encoded protein FMRP. Although macroorchidism and defects in neuronal architecture and function have been associated with lack of FMRP, the exact molecular mechanism underlying this disease remains unclear. We have reported previously that in the brain and testis of mice, FMRP specifically interacts with a distinct mRNA nuclear export factor NXF2 but not with its close relative NXF1, a ubiquitously expressed essential mRNA nuclear export factor. This interaction marked NXF2 as a putative functional partner of FMRP. Here, we demonstrate by immunoprecipitation and quantitative real-time RT-PCR that, in cultured mouse neuronal cells, both FMRP and NXF2 are present in Nxf1 mRNA-containing ribonucleoprotein particles. Further, we show that expression of NXF2 leads to the destabilization of Nxf1 mRNA and that this effect is abolished when Fmr1 expression is reduced by siRNA, arguing that both proteins collaborate to exert this effect. Importantly, these findings correlate well with our observations that in both mouse hippocampal neurons and male germ cells where the expression of FMRP and NXF2 is most prominent, the expression of NXF1 is relatively poorly expressed. Our studies thus identify Nxf1 mRNA as a likely biologically relevant in vivo target of both FMRP and NXF2 and implicate FMRP, in conjunction with NXF2, as a posttranscriptional regulator of a major mRNA export factor. Such regulation may prove important in the normal development and function of neurons as well as of male germ cells.germ cell ͉ neuron ͉ RNA stability

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The Nuclear Pore Complex and Nuclear Transport

Zagairy

Fichtman

Harel

2015

Encyclopedia of Life Sciences

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The nuclear pore complex (NPC) is an essential gateway between the cell nucleus and the cytoplasm. The NPC is formed by multiple copies of ∼30 different proteins called nucleoporins, which can be divided into scaffold, membrane‐anchored and barrier components. Thousands of phenylalanine‐glycine (FG) repeats, found in barrier nucleoporins, interact to form the selective permeability barrier of the NPC channel. Shuttling nuclear transport receptors are able to interact with these FG repeats and mediate the passage of large macromolecular cargoes through the barrier. Combinations of shuttling receptors, their adaptors and localisation signals in cargo molecules define a wide array of nuclear import and export pathways. Recent research has pointed to some dynamic features in NPC components, as well as a number of nucleoporin‐related human diseases which are characterised by highly cell‐type‐specific phenotypes. Key Concepts The nuclear pore complex (NPC) is a massive and elaborate structure formed by multiple copies of ∼30 different nucleoporins. The selective permeability barrier of the NPC is formed by hydrophobic interactions among FG repeats found in a large group of nucleoporins. Ions and small molecules are able to passively diffuse through the aqueous central channel of the NPC. Macromolecules transported through the NPC must contain specific targeting signals for nuclear import and nuclear export. Targeting signals are recognised by shuttling transport receptors which mediate the passage through the NPC channel by interacting with FG repeats. A small number of inherited diseases have been linked to mutations in human nucleoporins and are characterised by cell‐type‐specific phenotypes.

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Nucleocytoplasmic Transport: Integrating mRNA Production and Turnover with Export through the Nuclear Pore

Cited by 61 publications

References 98 publications

Recruitment of mRNA cleavage/polyadenylation machinery by the yeast chromatin protein Sin1p/Spt2p

Recruitment of mRNA cleavage/polyadenylation machinery by the yeast chromatin protein Sin1p/Spt2p

Fragile X mental retardation protein FMRP and the RNA export factor NXF2 associate with and destabilize Nxf1 mRNA in neuronal cells

The Nuclear Pore Complex and Nuclear Transport

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