Human ribosomal protein S13 regulates expression of its own gene at the splicing step by a feedback mechanism.
Human ribosomal protein S13 regulates expression of its own gene at the splicing step by a feedback mechanism.
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DOI：
10.1093/nar/gkm701
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发表时间：
2007
影响因子：
14.9
通讯作者：
Karpova GG
中科院分区：
文献类型：
--
作者：
Malygin AA;Parakhnevitch NM;Ivanov AV;Eperon IC;Karpova GG
核糖体蛋白（rp）基因的表达在多个水平上受到调控。在酵母中，两个基因通过蛋白质对前体mRNA剪接的反馈作用而自我调节。在这里，我们已经调查了类似的机制是否发生在真核生物更复杂和高度调控的剪接模式。比较哺乳动物和鸟类核糖体蛋白S13基因（RPS13）的序列，发现内含子1比其他内含子保守。用表达核糖体蛋白S13的小基因转染HEK 293细胞表明，内含子1的存在使表达降低了四倍。核糖体蛋白S13在体外可抑制rpS13前体mRNA片段内含子1的切除。这种蛋白质被证明能够特异性结合片段，并在5′和3′剪接位点附近的序列上提供保护以防止核糖核酸酶切割。结果表明，rpS13在哺乳动物细胞中的过量产生通过反馈机制干扰其自身前mRNA的剪接。
The expression of ribosomal protein (rp) genes is regulated at multiple levels. In yeast, two genes are autoregulated by feedback effects of the protein on pre-mRNA splicing. Here, we have investigated whether similar mechanisms occur in eukaryotes with more complicated and highly regulated splicing patterns. Comparisons of the sequences of ribosomal protein S13 gene (RPS13) among mammals and birds revealed that intron 1 is more conserved than the other introns. Transfection of HEK 293 cells with a minigene-expressing ribosomal protein S13 showed that the presence of intron 1 reduced expression by a factor of four. Ribosomal protein S13 was found to inhibit excision of intron 1 from rpS13 pre-mRNA fragment in vitro. This protein was shown to be able to specifically bind the fragment and to confer protection against ribonuclease cleavage at sequences near the 5′ and 3′ splice sites. The results suggest that overproduction of rpS13 in mammalian cells interferes with splicing of its own pre-mRNA by a feedback mechanism.