Exon ligation is proofread by the DExD/H-box ATPase Prp22p
Exon ligation is proofread by the DExD/H-box ATPase Prp22p
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DOI：
10.1038/nsmb1093
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发表时间：
2006-06-01
影响因子：
16.8
通讯作者：
Staley, Jonathan P.
中科院分区：
文献类型：
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作者：
Mayas, Rabiah M.;Maita, Hiroshi;Staley, Jonathan P.
为了产生信使RNA，剪接体从前体(前)-mRNA中切除内含子，并剪接两侧的外显子。为了建立保真度，剪接体区分异常的内含子，但目前对这种保真度机制的理解是有限的。在这里，我们表明，依赖于ATP的活性抑制了在任何内含子共有序列中具有突变的异常中间体的mRNA的形成。这种校对活性被破坏Prp22p的ATPase或RNA解旋酶活性的突变所禁用，Prp22p是一种保守的剪接体DExD/H-box ATPase。此外，冷敏感的prp22突变体允许在体内从突变的3‘剪接位点中间产物异常形成mRNA。我们得出结论，Prp22p除了在促进真实mRNA的释放方面具有已知的ATP依赖作用外，通常还抑制异常中间体的剪接。Prp22p的这种双重功能验证了一个通用模型，在该模型中，可以通过DExD/H-box ATPase来增强保真度。
To produce messenger RNA, the spliceosome excises introns from precursor (pre)-mRNA and splices the flanking exons. To establish fidelity, the spliceosome discriminates against aberrant introns, but current understanding of such fidelity mechanisms is limited. Here we show that an ATP-dependent activity represses formation of mRNA from aberrant intermediates having mutations in any of the intronic consensus sequences. This proofreading activity is disabled by mutations that impair the ATPase or RNA unwindase activity of Prp22p, a conserved spliceosomal DExD/H-box ATPase. Further, cold-sensitive prp22 mutants permit aberrant mRNA formation from a mutated 3' splice-site intermediate in vivo. We conclude that Prp22p generally represses splicing of aberrant intermediates, in addition to its known ATP-dependent role in promoting release of genuine mRNA. This dual function for Prp22p validates a general model in which fidelity can be enhanced by a DExD/H-box ATPase.