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Polypyrimidine Tract Binding Protein Modulates Efficiency of Polyadenylation

2004; Taylor & Francis; Volume: 24; Issue: 10 Linguagem: Inglês

10.1128/mcb.24.10.4174-4183.2004

1098-5549

Pedro Castelo‐Branco, André Furger, Matthew Wollerton, Christopher W. J. Smith, Alexandra Moreira, Nicholas Proudfoot,

RNA modifications and cancer

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.