scholarly journals Hypoxia May Increase Rat Insulin mRNA Levels by Promoting Binding of the Polypyrimidine Tract-binding Protein (PTB) to the Pyrimidine-rich Insulin mRNA 3′-Untranslated Region

2002 ◽  
Vol 8 (5) ◽  
pp. 263-272 ◽  
Author(s):  
Linda Tillmar ◽  
Nils Welsh
Keyword(s):  
Untranslated Region ◽  
Binding Protein ◽  
Mrna Levels ◽  
Polypyrimidine Tract ◽  
Polypyrimidine Tract Binding ◽  
Polypyrimidine Tract Binding Protein ◽  
Insulin Mrna

A High Affinity Binding Site for the Polypyrimidine Tract Binding Protein (PTB) Is Located in the 5'-Untranslated Region of the Rat Proteinase α1-Inhibitor 3 Variant I Gene

1999 ◽  
Vol 380 (10) ◽  
pp. 1217-1223 ◽  
Author(s):  
Stefan Sickinger ◽  
Michael Schweizer
Keyword(s):  
Untranslated Region ◽  
Binding Protein ◽  
Upstream Region ◽  
Polypyrimidine Tract ◽  
Complementary Sequence ◽  
Polypyrimidine Tract Binding ◽  
High Affinity ◽  
Polypyrimidine Tract Binding Protein ◽  
Sense Strand ◽  
I Gene

Abstract As a first step towards understanding the mechanism underlying the differential gene expression of the two variants of the rat proteinase-inhibitor α1-Inhibitor 3 (α1I3) corresponding genomic clones were isolated. The 100% similarity between the sequence of one genomic clone and that of the α1-I3 variant I cDNA strongly suggested that its 5′-sequence represented the upstream region of the corresponding gene. Several putative cis-regulatory elements were identified as well as a polypyrimidine tract located between the transcription start site of the α1-I3 variant I mRNA and the AUG codon. The polypyrimidine tract functions as a positive cis-element in a heterologous promoter. By electrophoretic mobility shift assays (EMSA) we have shown that a GST (glutathione S-transferase) fusion of the rat polypyrimidine tract binding protein (PTB) has a high affinity for the pyrimidine-rich sense strand but not for the complementary sequence of the 5′-untranslated region of the α1-I3 variant I gene.

scholarly journals Polypyrimidine Tract Binding Protein Modulates Efficiency of Polyadenylation

2004 ◽  
Vol 24 (10) ◽  
pp. 4174-4183 ◽  
Author(s):  
Pedro Castelo-Branco ◽  
Andre Furger ◽  
Matthew Wollerton ◽  
Christopher Smith ◽  
Alexandra Moreira ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Mrna Expression ◽  
Binding Protein ◽  
Upstream Sequence ◽  
Mrna Levels ◽  
Polypyrimidine Tract ◽  
Sequence Element ◽  
Polypyrimidine Tract Binding ◽  
Positive Effects ◽  
Polypyrimidine Tract Binding Protein

ABSTRACT Polypyrimidine tract binding protein (PTB) is a major hnRNP protein with multiple roles in mRNA metabolism, including regulation of alternative splicing and internal ribosome entry site-driven translation. We show here that a fourfold overexpression of PTB results in a 75% reduction of mRNA levels produced from transfected gene constructs with different polyadenylation signals (pA signals). This effect is due to the reduced efficiency of mRNA 3′ end cleavage, and in vitro analysis reveals that PTB competes with CstF for recognition of the pA signal's pyrimidine-rich downstream sequence element. This may be analogous to its role in alternative splicing, where PTB competes with U2AF for binding to pyrimidine-rich intronic sequences. The pA signal of the C2 complement gene unusually possesses a PTB-dependent upstream sequence, so that knockdown of PTB expression by RNA interference reduces C2 mRNA expression even though PTB overexpression still inhibits polyadenylation. Consequently, we show that PTB can act as a regulator of mRNA expression through both its negative and positive effects on mRNA 3′ end processing.

Sign in / Sign up

Export Citation Format

Share Document