R&D Department, BGI Genomics, BGI-Shenzhen, Shenzhen 518083, China.
Institute of Reproductive Medicine, Nantong University School of Medicine, Nantong University, Nantong 226001, Jiangsu, China.
Development. 2022 Jun 15;149(12). doi: 10.1242/dev.199573. Epub 2022 Jun 16.
As one of the post-transcriptional regulatory mechanisms, uncoupling of transcription and translation plays an essential role in development and adulthood physiology. However, it remains elusive how thousands of mRNAs get translationally silenced while stability is maintained for hours or even days before translation. In addition to oocytes and neurons, developing spermatids display significant uncoupling of transcription and translation for delayed translation. Therefore, spermiogenesis represents an excellent in vivo model for investigating the mechanism underlying uncoupled transcription and translation. Through full-length poly(A) deep sequencing, we discovered dynamic changes in poly(A) length through deadenylation and re-polyadenylation. Deadenylation appeared to be mediated by microRNAs (miRNAs), and transcripts with shorter poly(A) tails tend to be sequestered into ribonucleoprotein (RNP) granules for translational repression and stabilization. In contrast, re-polyadenylation might allow for translocation of the translationally repressed transcripts from RNP granules to polysomes. Overall, our data suggest that miRNA-dependent poly(A) length control represents a previously unreported mechanism underlying uncoupled translation and transcription in haploid male mouse germ cells.
作为转录后调控机制之一,转录和翻译的解偶联在发育和成年生理学中起着至关重要的作用。然而,数千个 mRNA 在翻译前保持数小时甚至数天的稳定性,而其翻译却被沉默,其具体机制仍不清楚。除卵母细胞和神经元外,发育中的精母细胞也表现出明显的转录和翻译解偶联,以延迟翻译。因此,精子发生代表了研究转录和翻译解偶联机制的极好的体内模型。通过全长 poly(A) 深度测序,我们发现通过去腺苷酸化和再腺苷酸化,poly(A) 长度会发生动态变化。去腺苷酸化似乎是由 microRNAs (miRNAs) 介导的,并且具有较短 poly(A) 尾巴的转录本倾向于被隔离到核糖核蛋白 (RNP) 颗粒中,以进行翻译抑制和稳定。相比之下,再腺苷酸化可能允许翻译抑制的转录本从 RNP 颗粒易位到多核糖体。总的来说,我们的数据表明,miRNA 依赖性 poly(A) 长度控制代表了以前未报道的在雄性小鼠生殖细胞中翻译和转录解偶联的机制。