mRNA maturation by two-step trans-splicing/polyadenylation processing in trypanosomes

Adriana V. Jäger, Javier G. De Gaudenzi, Alejandro Cassola, Iván D'Orso, Alberto C. Frasch

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2035-2042
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number7
DOIs
Publication statusPublished - Feb 13 2007

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Keywords

  • Gene expression
  • Posttranscriptional regulation
  • RNA processing

ASJC Scopus subject areas

  • Genetics
  • General

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