Nuclear exchange of the U1 and U2 snRNP-specific proteins.

Feeney, Robert J.; Zieve, Gary W.

doi:10.1083/jcb.110.4.871

Cited by 29 publications

(11 citation statements)

References 51 publications

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“…they are transported separately from the rest of the snRNP (20). The study in Xenopus laevis oocytes confirmed that U1A is targeted to the nucleus independently of its association with snRNA (21).…”

supporting

confidence: 52%

Nuclear Import of the U1A Splicesome Protein Is Mediated by Importin α/β and Ran in Living Mammalian Cells

Hieda

Tachibana

Fukumoto

et al. 2001

Journal of Biological Chemistry

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U1A is a component of the uracil-rich small nuclear ribonucleoprotein. The molecular mechanism of nuclear import of U1A was investigated in vivo and in vitro. When recombinant deletion mutants of U1A are injected into the BHK21 cell cytoplasm, the nuclear localization signal (NLS) of U1A is found in the N-terminal half of the central domain (residues 100 -144 in mouse U1A). In an in vitro assay, it was found that the U1A-NLS accumulated in only a portion of the nuclei in the absence of cytosolic extract. In contrast, the addition of importin ␣/␤ and Ran induced the uniform nuclear accumulation of U1A-NLS in all cells. Furthermore, U1A was found to bind the C-terminal portion of importin ␣. In addition, the in vitro nuclear migration of full-length U1A was found to be exclusively dependent on importin ␣/␤ and Ran. Moreover, in living cells, the full-length U1A accumulated in the nucleus in a Ran-dependent manner, and nuclear accumulation was inhibited by the importin ␤ binding domain of importin ␣. These results suggest that the nuclear import of U1A is mediated by at least two distinct pathways, an importin ␣/␤ and Ran-dependent and an -independent pathway in permeabilized cells, and that the latter pathway may be suppressed in intact cells.Cellular activities in eukaryotic cells are coordinated via the continuous and bi-directional transport of macromolecules between the nucleus and the cytoplasm, which occurs through the nuclear pore complexes (NPCs).1 The translocation of proteins through the NPCs is mediated by an active and selective mechanism that is controlled by saturable receptors and signals that are termed nuclear localization signals (NLSs) and nuclear export signals (reviewed in Refs. 1 and 2).The best characterized active nuclear protein import is mediated by a basic type NLS, referred to as "classical NLS," and which contains one or more clusters of basic amino acids. The import of substrates containing classical NLS such as SV40 large T antigen is initiated by the formation of an NLS-dependent complex with importin ␣/␤ in the cytoplasm, which is referred to as the nuclear pore-targeting complex. Importin ␣ recognizes the NLS and binds to importin ␤ via its N-terminal sequences, which are rich in basic amino acids, and is referred to as the importin ␤ binding (IBB) domain (3). Importin ␤ accounts for the targeting of the complex to the NPC. In addition to this classical import pathway, several different types of pathways have been identified, which involve importin ␤ or importin ␤ family members that bind directly to their cognate cargoes without importin ␣ (4 -6).It has been shown that there are at least five different forms of importin ␣ in the human and mouse that display significantly different tissue expression patterns (7, 8). It has been also shown that these importin ␣ isoforms interact differentially with specific NLS (9 -11). As evidenced by the primary sequences, these molecules can be grouped into three subfamilies, which are referred to Rch1, NPI-1, and Qip1, and which show ϳ50% amino...

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supporting

confidence: 52%

Nuclear Import of the U1A Splicesome Protein Is Mediated by Importin α/β and Ran in Living Mammalian Cells

Hieda

Tachibana

Fukumoto

et al. 2001

Journal of Biological Chemistry

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“…The indications that A' protein may exchange into snRNPs as presented here and previously (10) and that A' may mediate protein-protein interactions within U2 snRNP suggests that U2 snRNPs are dynamic particles whose functions might be modulated by the presence of A' protein.…”

Section: Resultsmentioning

confidence: 96%

Leucine periodicity of U2 small nuclear ribonucleoprotein particle (snRNP) A' protein is implicated in snRNP assembly via protein-protein interactions.

Fresco¹,

Harper²,

Keene³

1991

Mol. Cell. Biol.

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Recombinant A' protein could be reconstituted into U2 small nuclear ribonucleoprotein particles (snRNPs) upon addition to HeLa cell extracts as determined by coimmunoprecipitation and particle density; however, direct binding to U2 RNA could not be demonstrated except in the presence of the U2 snRNP B" protein.Mutational analysis indicated that a central core region of A' was required for particle reconstitution. This region consists of five tandem repeats of approximately 24 amino acids each that exhibit a periodicity of leucine and asparagine residues that is distinct from the leucine zipper. Similar leucine-rich (Leu-Leu motif) repeats are characteristic of a diverse array of soluble and membrane-associated proteins from yeasts to humans but have not been reported previously to reside in nuclear proteins. Several of these proteins, including Toll, chaoptin, RNase/angiogenin inhibitors, lutropin-choriogonadotropin receptor, carboxypeptidase N, adenylyl cyclase, CD14, and human immunodeficiency virus type 1 Rev, may be involved in protein-protein interactions. Our findings suggest that in cell extracts the Leu-Leu motif of A' is required for reconstitution with U2 snRNPs and perhaps with other components involved in splicing through protein-protein interactions.

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“…The two largest U1-specific proteins, U1-70K and U1-A, bind directly to the U1 snRNA while the U1-C protein is attached through protein-protein interactions with U1-70K and Sm proteins (Nelissen et al 1994). U1-A and U1-C are imported to the nucleus independently of the U1 snRNA (Jantsch and Gall 1992;Kambach and Mattaj 1992), indicating that U1 snRNP assembly occurs in the nucleus (Feeney and Zieve 1990). The role of CBs in this process is not clear.…”

Section: U1 Snrnpmentioning

confidence: 97%

The Cajal body: a meeting place for spliceosomal snRNPs in the nuclear maze

2006

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Spliceosomal small nuclear ribonucleoprotein particles (snRNPs) are essential pre-mRNA splicing factors that consist of small nuclear RNAs (snRNAs) complexed with specific sets of proteins. A considerable body of evidence has established that snRNP assembly is accomplished after snRNA synthesis in the nucleus through a series of steps involving cytoplasmic and nuclear phases. Recent work indicates that snRNPs transiently localize to the Cajal body (CB), a nonmembrane-bound inclusion present in the nuclei of most cells, for the final steps in snRNP maturation, including snRNA base modification, U4/U6 snRNA annealing, and snRNA-protein assembly. Here, we review these findings that suggest a crucial role for CBs in the spliceosome cycle in which production of new snRNPs--and perhaps regenerated snRNPs after splicing--is promoted by the concentration of substrates in this previously mysterious subnuclear organelle. These insights allow us to speculate on the role of nuclear bodies in regulating the dynamics of RNP assembly to maintain a functional pool of factors available for key steps in gene expression.

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Nuclear exchange of the U1 and U2 snRNP-specific proteins.

Cited by 29 publications

References 51 publications

Nuclear Import of the U1A Splicesome Protein Is Mediated by Importin α/β and Ran in Living Mammalian Cells

Nuclear Import of the U1A Splicesome Protein Is Mediated by Importin α/β and Ran in Living Mammalian Cells

Leucine periodicity of U2 small nuclear ribonucleoprotein particle (snRNP) A' protein is implicated in snRNP assembly via protein-protein interactions.

The Cajal body: a meeting place for spliceosomal snRNPs in the nuclear maze

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