A Xenopus Protein Related to hnRNP I Has a Role in Cytoplasmic RNA Localization

Côté, Colette; Gautreau, Denise; Denegre, James M.; Kress, Tracy L.; Terry, Natalie A.; Mowry, Kimberly L.

doi:10.1016/s1097-2765(00)80345-7

Cited by 219 publications

(242 citation statements)

References 44 publications

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“…More recently, PTB was also found associated with the 3'UTR of the ATP synthase b-subunit, where it helps enhancing translation in a cap-independent manner [62]. In addition to its role in splicing and translation regulation, PTB is implicated in 3'-end processing [63,64], localization [65,66], and stability [67 -75] of various cellular mRNAs. In these systems, PTB acts through pyrimidine-tract binding sites within 5' and/or 3'UTRs.…”

Section: The Many Functions Of Polypyrimidine Tract Binding Proteinmentioning

confidence: 99%

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Structure-function relationships of the polypyrimidine tract binding protein

Auweter

Allain

2007

Cell. Mol. Life Sci.

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Abstract. The polypyrimidine tract binding protein (PTB) is a 58-kDa RNA binding protein involved in multiple aspects of mRNA metabolism including splicing regulation, polyadenylation, 3'end formation, internal ribosomal entry site-mediated translation, RNA localization and stability. PTB contains four RNA recognition motifs (RRMs) separated by three linkers. In this review we summarize structural information on PTB in solution that has been gathered during the past 7 years using NMR spectroscopy and small-angle X-ray scattering. The structures of all RRMs of PTB in their free state and in complex with short pyrimidine tracts, as well as a structural model of PTB RRM2 in complex with a peptide, revealed unusual structural features that provided new insights into the mechanisms of action of PTB in the different processes of RNA metabolism and in particular splicing regulation.

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Section: The Many Functions Of Polypyrimidine Tract Binding Proteinmentioning

confidence: 99%

“…Vol. 65,2008 Review Article 521 to function through an interaction with PTB, and might facilitate the identification of novel PTB targets. For example, many studies identified PTB binding sites by boundary analyses, gel shift experiments and cross-linking [10,15,22,32].…”

Section: How Can the Ptb Structures Explain Its Multiple Functionsmentioning

confidence: 99%

Structure-function relationships of the polypyrimidine tract binding protein

Auweter

Allain

2007

Cell. Mol. Life Sci.

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“…It is now widely believed that PTB functions as a negative regulator of pre-mRNA splicing, blocking the inclusion of numerous alternative exons into mRNA (Black, 2003), including its own exon . Besides roles in splicing, PTB has also been implicated in the regulation of other aspects of RNA metabolism, such as premRNA polyadenylation (Castelo-Branco et al, 2004), mRNA stability (Kosinski et al, 2003;Knoch et al, 2004), mRNA export from the nucleus (Zang et al, 2001) and mRNA localization in the cytoplasm (Cote et al, 1999). In addition, PTB is involved in the control of cap-independent translation driven by the internal ribosomal entry site (IRES).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro

et al. 2007

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Polypyrimidine tract-binding protein (PTB) is an RNAbinding protein with multiple functions in the regulation of RNA processing and IRES-mediated translation. We report here overexpression of PTB in a majority of epithelial ovarian tumors revealed by immunoblotting and tissue microarray (TMA) staining. By western blotting, we found that PTB was overexpressed in 17 out of 19 ovarian tumor specimens compared to their matchednormal tissues. By TMA staining, we found PTB expression in 38 out of 44 ovarian cancer cases but only in two out of nine normal adjacent tissues. PTB is also overexpressed in SV40 large T-antigen immortalized ovarian epithelial cells compared to normal human ovarian epithelial cells. Using doxycycline-inducible small interfering RNA technology, we found that knockdown of PTB expression in the ovarian tumor cell line A2780 substantially impaired tumor cell proliferation, anchorage-independent growth and in vitro invasiveness. These results suggest that overexpression of PTB is an important component of the multistep process of tumorigenesis, and might be required for the development and maintenance of epithelial ovarian tumors. Moreover, because of its novel role in tumor cell growth and invasiveness, shown here for the first time, PTB may be a novel therapeutic target in the treatment of ovarian cancer.

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“…RRM 1 and 2, in the N-terminal half of PTB, are required for PTB oligomerization and other protein-protein interactions, whereas RRM 3 and 4, in the C-terminal half of PTB, are necessary for the RNA-binding activity [11]. PTB is involved in multiple steps of pre-mRNA processing, including tissue-specific splicing [12], mRNA localization [13,14], regulation of polyadenylation [15], and transport of hepatitis B viral unspliced mRNA from nucleus to cytoplasm [16]. PTB localizes mainly in the nucleus and can shuttle between the nucleus and cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

Polypyrimidine-tract-binding Protein is a Component of the HCV RNA Replication Complex and Necessary for RNA Synthesis

et al. 2006

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The machinery for hepatitis C virus (HCV) RNA replication is still poorly characterized. The relationship between HCV RNA replication and translation is also not clear. We have previously shown that a cellular protein polypyrimidine-tract-binding protein (PTB) binds to HCV RNA at several different sites and modulates HCV translation in several ways. Here we show that PTB also participates in RNA replication. By bromouridine triphosphate (BrUTP) labeling and confocal microscopy of cells harboring an HCV replicon, we showed that the newly synthesized HCV RNA was localized to distinct structures in the cytoplasm, which also contain PTB. Membrane flotation analysis demonstrated that a fraction of cytoplasmic PTB was associated with a detergent-resistant membrane (DRM) structure consisting of lipid rafts, which also contained HCV nonstructural proteins and the human vesicle-associated membrane proteinassociated protein (hVAP-33). PTB in the DRM was resistant to protease digestion, but became sensitive after treatment with the raft-disrupting agents. PTB in the DRM consisted of multiple isoforms and the brain-specific paralog. By using small interfering RNA (siRNA) of PTB, we showed that silencing of the endogenous PTB reduced the replication of HCV RNA replicon. In a cell-free, de novo HCV RNA synthesis system, HCV RNA synthesis was inhibited by anti-PTB antibody. These studies together indicated that PTB is a part of the HCV RNA replication complex and participates in viral RNA synthesis. Thus, PTB has dual functions in HCV life cycle, including translation and RNA replication.

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A Xenopus Protein Related to hnRNP I Has a Role in Cytoplasmic RNA Localization

Cited by 219 publications

References 44 publications

Structure-function relationships of the polypyrimidine tract binding protein

Structure-function relationships of the polypyrimidine tract binding protein

Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro

Polypyrimidine-tract-binding Protein is a Component of the HCV RNA Replication Complex and Necessary for RNA Synthesis

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