Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany.
Gene Expression and Signaling Group, Institute of Cell Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Nucleic Acids Res. 2022 Jun 24;50(11):6001-6019. doi: 10.1093/nar/gkab1189.
Translational readthrough (TR) occurs when the ribosome decodes a stop codon as a sense codon, resulting in two protein isoforms synthesized from the same mRNA. TR has been identified in several eukaryotic organisms; however, its biological significance and mechanism remain unclear. Here, we quantify TR of several candidate genes in Drosophila melanogaster and characterize the regulation of TR in the large Maf transcription factor Traffic jam (Tj). Using CRISPR/Cas9-generated mutant flies, we show that the TR-generated Tj isoform is expressed in a subset of neural cells of the central nervous system and is excluded from the somatic cells of gonads. Control of TR in Tj is critical for preservation of neuronal integrity and maintenance of reproductive health. The tissue-specific distribution of a release factor splice variant, eRF1H, plays a critical role in modulating differential TR of leaky stop codon contexts. Fine-tuning of gene regulatory functions of transcription factors by TR provides a potential mechanism for cell-specific regulation of gene expression.
翻译通读（TR）是指核糖体将终止密码子解码为有意义的密码子，从而从同一 mRNA 合成两种蛋白质异构体的过程。TR 在几种真核生物中已被识别，但它的生物学意义和机制仍不清楚。在这里，我们对果蝇中的几个候选基因的 TR 进行了定量，并对大 Maf 转录因子 Traffic jam（Tj）的 TR 调节进行了特征描述。使用 CRISPR/Cas9 生成的突变蝇，我们表明 TR 产生的 Tj 异构体在中枢神经系统的部分神经细胞中表达，而在性腺的体细胞中则被排除。Tj 中 TR 的控制对于保持神经元完整性和生殖健康至关重要。释放因子剪接变体 eRF1H 的组织特异性分布在调节渗漏终止密码子背景的差异 TR 中起着关键作用。通过 TR 对转录因子基因调控功能的精细调节为细胞特异性基因表达调控提供了一种潜在的机制。
