Insights into the Regulation of mRNA Processing of Polycistronic Transcripts Mediated by DRBD4/PTB2, a Trypanosome Homolog of the Polypyrimidine Tract‐Binding Protein

Abstract

Trypanosomes regulate gene expression mostly by posttranscriptional mechanisms, including control of mRNA turnover and translation efficiency. This regulation is carried out via certain elements located at the 3'-untranslated regions of mRNAs, which are recognized by RNA-binding proteins. In trypanosomes, trans-splicing is of central importance to control mRNA maturation. We have previously shown that TcDRBD4/PTB2, a trypanosome homolog of the human polypyrimidine tract-binding protein splicing regulator, interacts with the intergenic region of one specific dicistronic transcript, referred to as TcUBP (and encoding for TcUBP1 and TcUBP2, two closely kinetoplastid-specific proteins). In this work, a survey of TcUBP RNA processing revealed certain TcDRBD4/PTB2-regulatory elements within its intercistronic region, which are likely to influence the trans-splicing rate of monocistronic-derived transcripts. Furthermore, TcDRBD4/PTB2 overexpression in epimastigote cells notably decreased both UBP1 and UBP2 protein expression. This type of posttranscriptional gene regulatory mechanism could be extended to other transcripts as well, as we identified several other RNA precursor molecules that specifically bind to TcDRBD4/PTB2. Altogether, these findings support a model in which TcDRBD4/PTB2-containing ribonucleoprotein complexes can prevent trans-splicing. This could represent another stage of gene expression regulation mediated by the masking of trans-splicing/polyadenylation signals.