Polypyrimidine tract binding protein (PTB) associates with intronic and exonic domains to squelch nuclear export of unspliced RNA

Retention of unspliced pre-messenger RNA (pre-mRNA) in the nucleus is essential for cell survival. Available nuclear factors must recognize and discern between diverse export signals present in pre-mRNA to establish an export inhibitory complex. We found that polypyrimidine domains present in both intron and exon were important for export inhibition of a minigene transcript based on hepatitis B virus pregenomic RNA. Overexpression of PTB drastically reduced export and presence of RRM4 domain seemed critical. This inhibitory network overrode stimulation from an exonic export-facilitating element. We posit that binding of PTB to multiple loci on pre-mRNA regulates nuclear retention.