Biozentrum, University of Basel, 4056 Basel, Switzerland.
Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Development. 2021 Dec 15;148(24). doi: 10.1242/dev.200027. Epub 2021 Dec 16.
mRNA localization is an evolutionarily widespread phenomenon that can facilitate subcellular protein targeting. Extensive work has focused on mRNA targeting through 'zip-codes' within untranslated regions (UTRs), whereas much less is known about translation-dependent cues. Here, we examine mRNA localization in Caenorhabditis elegans embryonic epithelia. From an smFISH-based survey, we identified mRNAs associated with the cell membrane or cortex, and with apical junctions in a stage- and cell type-specific manner. Mutational analyses for one of these transcripts, dlg-1/discs large, revealed that it relied on a translation-dependent process and did not require its 5' or 3' UTRs. We suggest a model in which dlg-1 transcripts are co-translationally localized with the nascent protein: first the translating complex goes to the cell membrane using sequences located at the C-terminal/3' end, and then apically using N-terminal/5' sequences. These studies identify a translation-based process for mRNA localization within developing epithelia and determine the necessary cis-acting sequences for dlg-1 mRNA targeting.
mRNA 定位是一种广泛存在于进化过程中的现象,它可以促进亚细胞蛋白质靶向。大量的工作集中在通过非翻译区(UTR)中的“密码子”来实现 mRNA 靶向,而对依赖翻译的线索知之甚少。在这里,我们检查了秀丽隐杆线虫胚胎上皮中的 mRNA 定位。通过基于 smFISH 的调查,我们以阶段和细胞类型特异性的方式鉴定了与细胞膜或皮质以及与顶端连接相关的 mRNA。对其中一种转录本 dlg-1/discs large 的突变分析表明,它依赖于依赖翻译的过程,并且不需要其 5' 或 3' UTR。我们提出了一个模型,其中 dlg-1 转录本与新生蛋白共翻译定位:首先,翻译复合物使用位于 C 末端/3' 端的序列到达细胞膜,然后使用 N 末端/5' 序列到达顶端。这些研究确定了在发育中的上皮细胞中 mRNA 定位的基于翻译的过程,并确定了 dlg-1 mRNA 靶向所需的顺式作用序列。