Proteogenomic identification of translated small open reading frames in humans has revealed thousands of microproteins, or polypeptides of fewer than 100 amino acids, that were previously invisible to geneticists. Hundreds of microproteins have been shown to be essential for cell growth and proliferation, and many regulate macromolecular complexes. One such regulatory microprotein is NBDY, a 68-amino acid component of the human cytoplasmic RNA decapping complex. Heterologously expressed NBDY was previously reported to regulate cytoplasmic ribonucleoprotein granules known as P-bodies and reporter gene stability, but the global effect of endogenous NBDY on the cellular transcriptome remained undefined. In this work, we demonstrate that endogenous NBDY directly interacts with the human RNA decapping complex through EDC4 and DCP1A and localizes to P-bodies. Global profiling of RNA stability changes in NBDY knockout (KO) cells reveals dysregulated stability of more than 1400 transcripts. DCP2 substrate transcript half-lives are both increased and decreased in NBDY KO cells, which correlates with 5′ UTR length. NBDY deletion additionally alters the stability of non-DCP2 target transcripts, possibly as a result of downregulated expression of nonsense-mediated decay factors in NBDY KO cells. We present a comprehensive model of the regulation of RNA stability by NBDY.

中文翻译：

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NBDY 微蛋白调节细胞 RNA 脱帽

人类翻译的小开放阅读框的蛋白质基因组学鉴定揭示了数千种微生物蛋白质，或少于 100 个氨基酸的多肽，这些以前遗传学家是看不到的。数以百计的微蛋白已被证明对细胞生长和增殖至关重要，并且许多微蛋白调节大分子复合物。一种这样的调节微生物蛋白是 NBDY，它是人细胞质 RNA 脱帽复合物的 68 个氨基酸组分。先前有报道称，异源表达的 NBDY 可调节称为 P 体和报告基因稳定性的细胞质核糖核蛋白颗粒，但内源性 NBDY 对细胞转录组的整体影响仍未确定。在这项工作中，我们证明内源性 NBDY 通过 EDC4 和 DCP1A 直接与人类 RNA 脱帽复合物相互作用并定位于 P 体。RNA稳定性变化的全局分析NBDY敲除 (KO) 细胞揭示了 1400 多个转录本的失调稳定性。DCP2 底物转录半衰期在NBDY KO 细胞中增加和减少，这与 5' UTR 长度相关。NBDY缺失还会改变非 DCP2 靶转录物的稳定性，这可能是由于NBDY KO 细胞中无义介导的衰变因子表达下调所致。我们提出了 NBDY 调节 RNA 稳定性的综合模型。