Retrograde transfer RNA nuclear import provides a new level of tRNA quality control in Saccharomyces cerevisiae
Retrograde transfer RNA nuclear import provides a new level of tRNA quality control in Saccharomyces cerevisiae
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DOI：
10.1073/pnas.1316579110
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发表时间：
2013-12-24
影响因子：
11.1
通讯作者：
Hopper, Anita K.
中科院分区：
文献类型：
--
作者：
Kramer, Emily B.;Hopper, Anita K.
在真核生物中，转移RNA(TRNAs)在细胞核内转录，但在细胞质中发挥作用；因此，tRNA在细胞内的运动被认为是单向的--从细胞核到细胞质。现在已经知道，成熟的tRNA也通过逆行tRNA核导入从细胞质逆行移动到细胞核，这一过程从酵母到脊椎动物都是保守的。这种tRNA核进口的生物学意义尚不完全清楚。我们假设逆行tRNA核输入可能在校对tRNAs方面发挥作用，以确保只有合适的tRNAs驻留在细胞质中，并与翻译机制相互作用。在这里，我们确定了酵母中两种主要类型的异常tRNA：5‘，3’末端延伸的剪接tRNA和低修饰性tRNA。我们发现，这两种类型的异常tRNAs都积累在tRNA核运输缺陷的突变细胞中，这表明它们正常地输入到细胞核中，并被修复或降解。逆行途径与细胞质快速tRNA衰变途径并行发挥作用，以监测tRNA的质量，如果细胞缺乏这两条途径，就不能存活。我们的数据支持这样的假设，即逆行过程提供了新发现的tRNA质量控制水平，作为一条监测前tRNA的末端加工和成熟tRNA的修饰状态的途径。
In eukaryotes, transfer RNAs (tRNAs) are transcribed in the nucleus yet function in the cytoplasm; thus, tRNA movement within the cell was believed to be unidirectional-from the nucleus to the cytoplasm. It is now known that mature tRNAs also move in a retrograde direction from the cytoplasm to the nucleus via retrograde tRNA nuclear import, a process that is conserved from yeast to vertebrates. The biological significance of this tRNA nuclear import is not entirely clear. We hypothesized that retrograde tRNA nuclear import might function in proofreading tRNAs to ensure that only proper tRNAs reside in the cytoplasm and interact with the translational machinery. Here we identify two major types of aberrant tRNAs in yeast: a 5', 3' end-extended, spliced tRNA and hypomodified tRNAs. We show that both types of aberrant tRNAs accumulate in mutant cells that are defective in tRNA nuclear traffic, suggesting that they are normally imported into the nucleus and are repaired or degraded. The retrograde pathway functions in parallel with the cytoplasmic rapid tRNA decay pathway previously demonstrated to monitor tRNA quality, and cells are not viable if they lack both pathways. Our data support the hypothesis that the retrograde process provides a newly discovered level of tRNA quality control as a pathway that monitors both end processing of pre-tRNAs and the modification state of mature tRNAs.