mRNA maturation by two-step trans-splicing/polyadenylation processing in trypanosomes.
Trypanosomes are unique eukaryotic cells, in that they virtually lack mechanisms to control gene expression at the transcriptional level. These microorganisms mostly control protein synthesis by posttranscriptional regulation processes, like mRNA stabilization and degradation. Transcription in these cells is polycistronic. Tens to hundreds of protein-coding genes of unrelated function are arrayed in long clusters on the same DNA strand. Polycistrons are cotranscriptionally processed by trans-splicing at the 5' end and polyadenylation at the 3' end, generating monocistronic units ready for degradation or translation. In this work, we show that some trans-splicing/polyadenylation sites may be skipped during normal polycistronic processing. As a consequence, dicistronic units or monocistronic transcripts having long 3' UTRs are produced. Interestingly, these unspliced transcripts can be processed into mature mRNAs by the conventional trans-splicing/polyadenylation events leading to translation. To our knowledge, this is a previously undescribed mRNA maturation by trans-splicing uncoupled from transcription. We identified an RNA-recognition motif-type protein, homologous to the mammalian polypyrimidine tract-binding protein, interacting with one of the partially processed RNAs analyzed here that might be involved in exon skipping. We propose that splice-site skipping might be part of a posttranscriptional mechanism to regulate gene expression in trypanosomes, through the generation of premature nontranslatable RNA molecules.
Jäger
Adriana V
AV
Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico Chascomus, Universidad Nacional de San Martín-Consejo Nacional de Investigaciones Científicas y Técnicas, Provincia de Buenos Aires, Argentina.
De Gaudenzi
Javier G
JG
Cassola
Alejandro
A
D'Orso
Iván
I
Frasch
Alberto C
AC
D020413:3' Untranslated Regions; D000818:Animals; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D026723:Polyadenylation; D012323:RNA Processing, Post-Transcriptional; D016053:RNA, Protozoan / Q000235:genetics*; D020040:Trans-Splicing; D014345:Trypanosoma / Q000235:genetics*
D020413:3' Untranslated Regions; D016053:RNA, Protozoan