scholarly journals Far upstream element binding protein 2 interacts with enterovirus 71 internal ribosomal entry site and negatively regulates viral translation

2008 ◽  
Vol 37 (1) ◽  
pp. 47-59 ◽  
Author(s):  
Jing-Yi Lin ◽  
Mei-Ling Li ◽  
Shin-Ru Shih
Keyword(s):  
Binding Protein ◽  
Internal Ribosomal Entry Site ◽  
Enterovirus 71 ◽  
Entry Site ◽  
Viral Translation ◽  
Element Binding Protein ◽  
Upstream Element ◽  
Ribosomal Entry

scholarly journals Enterovirus 71 Infection Cleaves a Negative Regulator for Viral Internal Ribosomal Entry Site-Driven Translation

2013 ◽  
Vol 87 (7) ◽  
pp. 3828-3838 ◽  
Author(s):  
L.-L. Chen ◽  
Y.-A. Kung ◽  
K.-F. Weng ◽  
J.-Y. Lin ◽  
J.-T. Horng ◽  
...  
Keyword(s):  
Internal Ribosomal Entry Site ◽  
Enterovirus 71 ◽  
Negative Regulator ◽  
Entry Site ◽  
Ribosomal Entry ◽  
Enterovirus 71 Infection

scholarly journals Polypyrimidine Tract-Binding Protein Enhances the Internal Ribosomal Entry Site-Dependent Translation of p27Kip1 mRNA and Modulates Transition from G1 to S Phase

2005 ◽  
Vol 25 (4) ◽  
pp. 1283-1297 ◽  
Author(s):  
Sungchan Cho ◽  
Jong Heon Kim ◽  
Sung Hoon Back ◽  
Sung Key Jang
Keyword(s):  
Cell Cycle ◽  
Binding Protein ◽  
Internal Ribosomal Entry Site ◽  
In Vitro Translation ◽  
Polypyrimidine Tract ◽  
Entry Site ◽  
Hl60 Cells ◽  
Polypyrimidine Tract Binding ◽  
Polypyrimidine Tract Binding Protein ◽  
Ribosomal Entry

ABSTRACT The p27Kip1 protein plays a critical role in the regulation of cell proliferation through the inhibition of cyclin-dependent kinase activity. Translation of p27Kip1 is directed by an internal ribosomal entry site (IRES) in the 5′ nontranslated region of p27Kip1 mRNA. Here, we report that polypyrimidine tract-binding protein (PTB) specifically enhances the IRES activity of p27Kip1 mRNA through an interaction with the IRES element. We found that addition of PTB to an in vitro translation system and overexpression of PTB in 293T cells augmented the IRES activity of p27Kip1 mRNA but that knockdown of PTB by introduction of PTB-specific small interfering RNAs (siRNAs) diminished the IRES activity of p27Kip1 mRNA. Moreover, the G1 phase in the cell cycle (which is maintained in part by p27Kip1) was shortened in cells depleted of PTB by siRNA knockdown. 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced differentiation in HL60 cells was used to examine PTB-induced modulation of p27Kip1 protein synthesis during differentiation. The IRES activity of p27Kip1 mRNA in HL60 cells was increased by TPA treatment (with a concomitant increase in PTB protein levels), but the levels of p27Kip1 mRNA remained unchanged. Together, these data suggest that PTB modulates cell cycle and differentiation, at least in part, by enhancing the IRES activity of p27Kip1 mRNA.

scholarly journals Replication of Poliovirus Requires Binding of the Poly(rC) Binding Protein to the Cloverleaf as Well as to the Adjacent C-Rich Spacer Sequence between the Cloverleaf and the Internal Ribosomal Entry Site

2007 ◽  
Vol 81 (18) ◽  
pp. 10017-10028 ◽  
Author(s):  
Hidemi Toyoda ◽  
David Franco ◽  
Kentaro Fujita ◽  
Aniko V. Paul ◽  
Eckard Wimmer
Keyword(s):  
Binding Protein ◽  
Position Effect ◽  
Internal Ribosomal Entry Site ◽  
Rna Replication ◽  
Cellular Protein ◽  
Entry Site ◽  
Stem Loop ◽  
Nontranslated Region ◽  
Ribosomal Entry

ABSTRACT The 5′ nontranslated region of poliovirus RNA contains two highly structured regions, the cloverleaf (CL) and the internal ribosomal entry site (IRES). A cellular protein, the poly(rC) binding protein (PCBP), has been reported to interact with the CL either alone or in combination with viral protein 3CDpro. The formation of the ternary complex is essential for RNA replication and, hence, viral proliferation. PCBP also interacts with stem-loop IV of the IRES, an event critical for the initiation of cap-independent translation. Until recently, no special function was assigned to a spacer region (nucleotides [nt] 89 to 123) located between the CL and the IRES. However, on the basis of our discovery that this region strongly affects the neurovirulent phenotype of poliovirus, we have embarked upon genetic and biochemical analyses of the spacer region, focusing on two clusters of C residues (C93-95 and C98-100) that are highly conserved among entero- and rhinoviruses. Replacement of all six C residues with A residues had no effect on translation in vitro but abolished RNA replication, leading to a lethal growth phenotype of the virus in HeLa cells. Mutation of the first group of C residues (C93-95) resulted in slower viral growth, whereas the C98-100A change had no significant effect on viability. Genetic analyses of the C-rich region by extensive mutagenesis and analyses of revertants revealed that two consecutive C residues (C94-95) were sufficient to promote normal growth of the virus. However, there was a distinct position effect of the preferred C residues. A 142-nt-long 5′-terminal RNA fragment including the CL and spacer sequences efficiently bound PCBP, whereas no PCBP binding was observed with the CL (nt 1 to 88) alone. Binding of PCBP to the 142-nt fragment was completely ablated after the two C clusters in the spacer were mutated to A clusters. In contrast, the same mutations had no effect on the binding of 3CDpro to the 142-nt RNA fragment. Stepwise replacement of the C residues with A residues resulted in impaired replication that covaried with weaker binding of PCBP in vitro. We conclude that PCBP has little, if any, binding affinity for the CL itself (nt 1 to 88) but requires additional nucleotides downstream of the CL for its function as an essential cofactor in poliovirus RNA replication. These data reveal a new essential function of the spacer between the CL and the IRES in poliovirus proliferation.

scholarly journals A Cellular RNA-Binding Protein Enhances Internal Ribosomal Entry Site-Dependent Translation through an Interaction Downstream of the Hepatitis C Virus Polyprotein Initiation Codon

2004 ◽  
Vol 24 (18) ◽  
pp. 7878-7890 ◽  
Author(s):  
Jong Heon Kim ◽  
Ki Young Paek ◽  
Sang Hoon Ha ◽  
Sungchan Cho ◽  
Kobong Choi ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Binding ◽  
Binding Protein ◽  
Internal Ribosomal Entry Site ◽  
Rna Binding Protein ◽  
Mrna Translation ◽  
Entry Site ◽  
Protein Coding ◽  
Ribosomal Entry

ABSTRACT Translational initiation of hepatitis C virus (HCV) mRNA occurs by internal entry of ribosomes into an internal ribosomal entry site (IRES) at the 5′ nontranslated region. A region encoding the N-terminal part of the HCV polyprotein has been shown to augment the translation of HCV mRNA. Here we show that a cellular protein, NS1-associated protein 1 (NSAP1), augments HCV mRNA translation through a specific interaction with an adenosine-rich protein-coding region within the HCV mRNA. The overexpression of NSAP1 specifically enhanced HCV IRES-dependent translation, and knockdown of NSAP1 by use of a small interfering RNA specifically inhibited the translation of HCV mRNA. An HCV replicon RNA capable of mimicking the HCV proliferation process in host cells was further used to confirm that NSAP1 enhances the translation of HCV mRNA. These results suggest the existence of a novel mechanism of translational enhancement that acts through the interaction of an RNA-binding protein with a protein coding sequence.

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