Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5′ to 3′ mRNA decay pathways in yeast
Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5′ to 3′ mRNA decay pathways in yeast
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DOI：
10.1016/s1097-2765(03)00446-5
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发表时间：
2003-12-01
期刊：
影响因子：
16
通讯作者：
Jacobson, A
中科院分区：
文献类型：
--
作者：
He, F;Li, XR;Jacobson, A
通过野生型、upf1Delta、nmd2Delta、upf3Delta、dcp1Delta和xrn1Delta细胞的表达谱鉴定了酵母无义介导的和5‘到3’mRNA衰退途径调控的转录本。这一分析表明，Upf1p、Nmd2p或Upf3p的失活对全球RNA积累具有相同的影响；Dcp1p或Xrn1p的失活对全球RNA积累表现出共同和独特的影响，但只导致一小部分转录本的上调；在UPF/NMD株中上调的大部分转录产物在dcp1Delta和xrn1Delta株中也有类似程度的上调。我们的结果定义了NMD调控的核心转录本，确定了NMD底物的几个新的结构类别，证明了即使在没有功能性NMD的情况下，含有无义的mRNAs也主要通过5‘到3’衰变途径降解，并表明酵母细胞中主要的mRNA衰变活性可能是3‘到5’衰变，而不是5‘到3’衰变。
Transcripts regulated by the yeast nonsense-mediated and 5' to 3' mRNA decay pathways were identified by expression profiling of wild-type, upf1Delta, nmd2Delta, upf3Delta, dcp1Delta, and xrn1Delta cells. This analysis revealed that inactivation of Upf1p, Nmd2p, or Upf3p has identical effects on global RNA accumulation; inactivation of Dcp1p or Xrn1p exhibits both common and unique effects on global RNA accumulation but causes upregulation of only a small fraction of transcripts; and the majority of transcripts upregulated in upf/nmd strains are also upregulated to similar extents in dcp1Delta and xrn1Delta strains. Our results define the core transcripts regulated by NMD, identify several novel structural classes of NMD substrates, demonstrate that nonsense-containing mRNAs are primarily degraded by the 5' to 3' decay pathway even in the absence of functional NMD, and indicate that 3' to 5' decay, not 5' to 3' decay, may be the major mRNA decay activity in yeast cells.