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
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
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DOI：
10.1074/jbc.275.14.10218
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发表时间：
2000-04-07
影响因子：
4.8
通讯作者：
Frasch, ACC
中科院分区：
文献类型：
--
作者：
Di Noia, JM;D'Orso, I;Frasch, ACC
克氏锥虫有一个复杂的粘蛋白基因家族，有500个成员，其中高变区在寄生虫的脊椎动物相关阶段优先表达。在这项工作中，报道了一个新的粘蛋白型基因家族，由两组独立串联的基因组成，具有非常短的开放阅读框，推导出的蛋白质结构共享N和C端，但在中心区域不同。一组重复序列一致为Lys- asn - thr (7)-Ser- thr (3)-Ser(Ser/Lys)-Ala-Pro，另一组重复序列为Asp-Gln-Thr(17-20)-Asn-Ala-Pro-Ala-Lys- asp - thr (5-7)-Asn-Ala-Pro-Ala-Lys。在这两种情况下，预期的成熟核心蛋白都在7 kDa左右，这两组分别命名为L和S，在基因组位点和mRNA的结构上存在差异，在3'-非翻译区具有不同的块，S和L组的mRNA水平最高，但它们表现出不同的发育调节模式。转录本的寿命很短，它们的稳态丰度在昆虫期随mRNA稳定性的增加而受到转录后的调节。富含au的序列，类似于在高等真核生物中引起mRMA不稳定的ARE动机，存在于转录本的3'-非翻译区。在转染实验中，该序列被证明对L组具有功能，以特定阶段的方式破坏其mRNA的稳定。此外，这个富含au的区域对翻译效率有影响。据我们所知，这是第一次在低等真核生物中报道功能性的依赖于ARE序列的转录后调控机制。
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-Lys. 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 mRMA 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.