The 5′ untranslated region (5′UTR) is critical in determining post-transcriptional control, which is partly mediated by short upstream open reading frames (uORFs) present in half of mammalian transcripts. uORFs are generally considered to provide functionally important repression of the main-ORF by engaging initiating ribosomes, but under specific environmental conditions such as cellular stress, uORFs can become essential to activate the translation of the main coding sequence. In addition, a growing number of uORF-encoded bioactive microproteins have been described, which have the potential to significantly increase cellular protein diversity. Here we review the diverse cellular contexts in which uORFs play a critical role and discuss the molecular mechanisms underlying their function and regulation. The progress over the last decades in dissecting uORF function suggests that the 5′UTR remains an exciting frontier towards understanding how the cellular proteome is shaped in health and disease.

5'非翻译区（5'UTR）在确定转录后控制中至关重要，这部分由一半哺乳动物转录本中的短上游开放阅读框（uORF）介导。通常认为uORF通过接合起始核糖体来提供对main-ORF的功能上重要的抑制，但是在特定的环境条件下，例如细胞应激，uORF可能成为激活主要编码序列翻译的必要条件。另外，已经描述了越来越多的uORF编码的生物活性微蛋白，其具有显着增加细胞蛋白多样性的潜力。在这里，我们回顾了uORF在其中发挥关键作用的各种细胞环境，并讨论了其功能和调控的分子机制。