title: AU-rich elements in the 3'-untranslated region of a new mucin-type gene family of Trypanosoma cruzi confers mRNA instability and modulates translation efficiency.
abstract: Trypanosoma cruzi has a complex mucin gene family of 500 members with hypervariable regions expressed preferentially in vertebrate associated stages of the parasite. In this work, a novel mucin-type gene family is reported, composed of two groups of genes organized in independent tandems and having very short open reading frames. The structures of deduced proteins share the N and C termini but differ in central regions. One group has repeats with the consensus Lys-Asn-Thr(7)-Ser-Thr(3)-Ser(Ser/Lys)-Ala-Pro and the other a Thr-rich sequence of the type Asp-Gln-Thr(17-20)-Asn-Ala-Pro-Ala-Lys-Asp-Thr(5-7)-Asn-Ala-Pro-Ala-L ys. In both cases, expected mature core proteins are around 7 kDa. Both groups, named L and S, respectively, differ in the structure of genomic loci and mRNA, with differential blocks in the 3'-untranslated region. The highest mRNA level for S and L groups are in the epimastigote stage but they show distinct developmentally regulated patterns. Transcripts are short lived and their steady-state abundance is regulated post-transcriptionally with increased mRNA stability in insect stage epimastigote. AU-rich sequences, similar to ARE motives known to cause mRNA instability in higher eukaryotes, are present in the 3'-untranslated region of the transcripts. In transfection experiments this sequence is shown to be functional for the L group destabilizing its mRNA in a stage-specific manner. Furthermore, an effect of this AU-rich region on translation efficiency is shown. To our knowledge, this is the first time that a functional ARE sequence-dependent post-transcriptional regulation mechanism is reported in a lower eukaryote.
authors.affiliation: Instituto de Investigaciones Biotecnológicas, Universidad Nacional de General San Martín, C.C. 30, 1650 San Martín, Pcia. de Buenos Aires, Argentina.
authors.forename: J M
authors.initials: JM
authors.lastname: Di Noia
authors.forename: I
authors.initials: I
authors.lastname: D'Orso
authors.forename: D O
authors.initials: DO
authors.lastname: Sánchez
authors.forename: A C
authors.initials: AC
authors.lastname: Frasch
mesh_terms: D020413:3' Untranslated Regions / Q000737:chemistry* / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001482:Base Composition; D020029:Base Pairing; D001483:Base Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017125:Genes, Protozoan; D006031:Glycosylation; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry / Q000235:genetics*; D005810:Multigene Family; D014176:Protein Biosynthesis; D021382:Protein Sorting Signals / Q000737:chemistry / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics*; D016053:RNA, Protozoan / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014349:Trypanosoma cruzi / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D009077:Mucins; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D016053:RNA, Protozoan