Uncoupling transcription and translation through miRNA-dependent poly(A) length control in haploid male germ cells

在单倍体雄性生殖细胞中通过 miRNA 依赖的 poly(A) 长度控制来解耦转录和翻译

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作者:Mei Guo, Chunhai Luo, Zhuqing Wang, Sheng Chen, Dayton Morris, Fengying Ruan, Zhichao Chen, Linfeng Yang, Xiongyi Wei, Chuanwen Wu, Bei Luo, Zhou Lv, Jin Huang, Dong Zhang, Cong Yu, Qiang Gao, Hongqi Wang, Ying Zhang, Fei Sun, Wei Yan, Chong Tang

Abstract

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.

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