Decoding the Function of Expansion Segments in Ribosomes
Decoding the Function of Expansion Segments in Ribosomes
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DOI：
10.1016/j.molcel.2018.11.023
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发表时间：
2018-12-20
期刊：
影响因子：
16
通讯作者：
Barna, Maria
中科院分区：
文献类型：
--
作者：
Fujii, Kotaro;Susanto, Teodorus Theo;Barna, Maria
扩展片段（ESs）是真核生物核糖体内的神秘插入物，其中最长的类似于在进化过程中长度和序列不同的触手样延伸，其功能在很大程度上未知。通过在酵母中选择性地改造rRNA，我们发现最大的ES之一，ES27L，在翻译保真度方面具有意想不到的功能。在ES27L的远端部分中具有缺失的核糖体具有增加的氨基酸错误掺入，以及通读和移码错误。通过采用定量质谱，我们进一步发现，ES27 L作为RNA支架，以促进保守的酶，蛋氨酸氨基肽酶（MetAP）的结合。我们发现，MetAP出乎意料地控制核糖体解码的准确性，这与通过与ES27L相互作用增加其酶功能相结合。这些发现揭示了核糖体的可变ES起着重要的功能作用，并作为调节跨进化翻译的蛋白质结合的平台。
Expansion segments (ESs) are enigmatic insertions within the eukaryotic ribosome, the longest of which resemble tentacle-like extensions that vary in length and sequence across evolution, with a largely unknown function. By selectively engineering rRNA in yeast, we find that one of the largest ESs, ES27L, has an unexpected function in translation fidelity. Ribosomes harboring a deletion in the distal portion of ES27L have increased amino acid misincorporation, as well as readthrough and frameshifting errors. By employing quantitative mass spectrometry, we further find that ES27L acts as an RNA scaffold to facilitate binding of a conserved enzyme, methionine amino peptidase (MetAP). We show that MetAP unexpectedly controls the accuracy of ribosome decoding, which is coupled to an increase in its enzymatic function through its interaction with ES27L. These findings reveal that variable ESs of the ribosome serve important functional roles and act as platforms for the binding of proteins that modulate translation across evolution.