Dasgupta Anwesha, Prensner John R
Chad Carr Pediatric Brain Tumor Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
NAR Cancer. 2024 May 20;6(2):zcae023. doi: 10.1093/narcan/zcae023. eCollection 2024 Jun.
The translation of RNA by ribosomes represents a central biological process and one of the most dysregulated processes in cancer. While translation is traditionally thought to occur exclusively in the protein-coding regions of messenger RNAs (mRNAs), recent transcriptome-wide approaches have shown abundant ribosome activity across diverse stretches of RNA transcripts. The most common type of this kind of ribosome activity occurs in gene leader sequences, also known as 5' untranslated regions (UTRs) of the mRNA, that precede the main coding sequence. Translation of these upstream open reading frames (uORFs) is now known to occur in upwards of 25% of all protein-coding genes. With diverse functions from RNA regulation to microprotein generation, uORFs are rapidly igniting a new arena of cancer biology, where they are linked to cancer genetics, cancer signaling, and tumor-immune interactions. This review focuses on the contributions of uORFs and their associated 5'UTR sequences to cancer biology.
核糖体对RNA的翻译是一个核心生物学过程，也是癌症中失调最为严重的过程之一。传统上认为翻译仅发生在信使RNA（mRNA）的蛋白质编码区域，但最近全转录组方法显示，在各种RNA转录本片段中都存在丰富的核糖体活性。这种核糖体活性最常见的类型发生在基因前导序列中，即mRNA的5'非翻译区（UTR），位于主要编码序列之前。现在已知这些上游开放阅读框（uORF）的翻译发生在所有蛋白质编码基因的25%以上。uORF具有从RNA调节到微蛋白生成等多种功能，正迅速开启癌症生物学的一个新领域，在这个领域中它们与癌症遗传学、癌症信号传导和肿瘤免疫相互作用相关联。本综述重点关注uORF及其相关的5'UTR序列对癌症生物学的贡献。
