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Truncated protein isoforms generate diversity of protein localization and function in yeast
Cell Systems ( IF 9.3 ) Pub Date : 2024-04-17 , DOI: 10.1016/j.cels.2024.03.005
Andrea L. Higdon , Nathan H. Won , Gloria A. Brar

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.

中文翻译:

截短的蛋白质亚型在酵母中产生蛋白质定位和功能的多样性

对 mRNA 上核糖体占用率进行全基因组测量使得能够凭经验识别翻译区域,但对与注释编码区域重叠的编码区域进行高置信度检测仍然具有挑战性。在此,我们报告了一种灵敏且强大的算法,该算法揭示了芽殖酵母中 388 个 N 末端截短蛋白质的翻译,比之前已知的多了 30 倍以上。我们对它们进行了广泛的实验验证并定义了两个类别。第一类缺乏大部分带注释的蛋白质,并且往往是由截短的转录物产生的。我们发现,Yap5 和 Pus1 这两种情况具有条件特异性调节作用,并且具有与其各自注释的亚型不同的功能。第二类截短的蛋白质亚型仅缺少注释蛋白质的一小部分区域,并且不太可能由替代转录物亚型产生。许多蛋白显示出与其注释对应物不同的亚细胞定位,代表了功能相同的蛋白质双重定位的通用策略。
更新日期:2024-04-17
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