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

DE GAUDENZI, JG#; JÄGER, AV; IZCOVICH, R; CAMPO, VA

JOURNAL OF EUKARYOTIC MICROBIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016

1066-5234

Trypanosomes regulate gene expression mostly by post-transcriptional 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 over-expression in epimastigote cells notably decreased both UBP1 and UBP2 protein expression. This type of post-transcriptional gene regulatory mechanism could be extended to other transcripts as well, since 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. #Corresponding author