Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell Syst. 2024 Apr 17;15(4):388-408.e4. doi: 10.1016/j.cels.2024.03.005.
Genome-wide measurement of ribosome occupancy on mRNAs has enabled empirical identification of translated regions, but high-confidence detection of coding regions that overlap annotated coding regions has remained challenging. Here, we report a sensitive and robust algorithm that revealed the translation of 388 N-terminally truncated proteins in budding yeast-more than 30-fold more than previously known. We extensively experimentally validated them and defined two classes. The first class lacks large portions of the annotated protein and tends to be produced from a truncated transcript. We show that two such cases, Yap5 and Pus1, have condition-specific regulation and distinct functions from their respective annotated isoforms. The second class of truncated protein isoforms lacks only a small region of the annotated protein and is less likely to be produced from an alternative transcript isoform. Many display different subcellular localizations than their annotated counterpart, representing a common strategy for dual localization of otherwise functionally identical proteins. A record of this paper's transparent peer review process is included in the supplemental information.
对 mRNA 上核糖体占据的全基因组进行测量，使人们能够对翻译区域进行实证识别，但要高置信度地检测与注释编码区重叠的编码区仍然具有挑战性。在这里，我们报告了一种灵敏且稳健的算法，该算法揭示了酿酒酵母中 388 种 N 端截断蛋白的翻译——比之前已知的数量多出 30 多倍。我们对它们进行了广泛的实验验证，并将其定义为两类。第一类缺乏注释蛋白的大部分，并且往往是由截断的转录本产生的。我们表明，这两种情况， Yap5 和 Pus1，具有特定条件的调控，并且具有与其各自注释异构体不同的功能。第二类截断蛋白异构体仅缺失注释蛋白的一小部分区域，不太可能来自替代的转录本异构体。许多蛋白的亚细胞定位与它们的注释对应物不同，这代表了一种常见的策略，用于将功能相同的蛋白进行双重定位。本文的透明同行评审过程记录包含在补充信息中。
