Sayani Shakir, Janis Michael, Lee Chrissie Young, Toesca Isabelle, Chanfreau Guillaume F
Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095-1569, USA.
Mol Cell. 2008 Aug 8;31(3):360-70. doi: 10.1016/j.molcel.2008.07.005.
Nonsense-mediated mRNA decay (NMD) eliminates transcripts carrying premature translation termination codons, but the role of NMD on yeast unspliced pre-mRNA degradation is controversial. Using tiling arrays, we show that many unspliced yeast pre-mRNAs accumulate in strains mutated for the NMD component Upf1p and the exonuclease Xrn1p. Intron identity and suboptimal splicing signals resulting in weak splicing were found to be important determinants in NMD targeting. In the absence of functional NMD, unspliced precursors accumulate in the cytoplasm, possibly in P-bodies. NMD can also complement RNase III-mediated nuclear degradation of unspliced RPS22B pre-mRNAs, degrades most unspliced precursors generated by a 5' splice site mutation in RPS10B, and limits RPS29B unspliced precursors accumulation during amino acid starvation. These results show that NMD has a wider impact than previously thought on the degradation of yeast-unspliced transcripts and plays an important role in discarding precursors of regulated or suboptimally spliced transcripts.
无义介导的mRNA降解（NMD）可消除携带提前翻译终止密码子的转录本，但NMD在酵母未剪接前体mRNA降解中的作用存在争议。利用平铺阵列，我们发现许多未剪接的酵母前体mRNA在NMD组分Upf1p和外切核酸酶Xrn1p发生突变的菌株中积累。内含子特性以及导致剪接效率低下的次优剪接信号被发现是NMD靶向作用的重要决定因素。在缺乏功能性NMD的情况下，未剪接的前体在细胞质中积累，可能在P小体中。NMD还可以补充核糖核酸酶III介导的未剪接RPS22B前体mRNA的核降解，降解由RPS10B中5'剪接位点突变产生的大多数未剪接前体，并在氨基酸饥饿期间限制RPS29B未剪接前体的积累。这些结果表明，NMD对酵母未剪接转录本降解的影响比以前认为的更广泛，并且在丢弃受调控或剪接次优转录本的前体方面发挥重要作用。
