State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; The University of Chinese Academy of Sciences, Beijing 100049, China.
The University of Chinese Academy of Sciences, Beijing 100049, China.
J Genet Genomics. 2017 Feb 20;44(2):95-106. doi: 10.1016/j.jgg.2016.12.007. Epub 2017 Jan 27.
In the sexually reproductive organisms, gametes are produced by meiosis following a limited mitotic amplification. However, the intrinsic program switching cells from mitotic to meiotic cycle is unclear. Alternative polyadenylation (APA) is a highly conserved means of gene regulation and is achieved by the RNA 3'-processing machinery to generate diverse 3'UTR profiles. In Drosophila spermatogenesis, we observed distinct profiles of transcriptome-wide 3'UTR between mitotic and meiotic cells. In mutant germ cells stuck in mitosis, 3'UTRs of hundreds of genes were consistently shifted. Remarkably, altering the levels of multiple 3'-processing factors disrupted germline's progression to meiosis, indicative of APA's active role in this transition. An RNA-binding protein (RBP) Tut could directly bind 3'UTRs of 3'-processing factors whose expressions were repressed in the presence of Tut-containing complex. Further, we demonstrated that this RBP complex could execute the repression post-transcriptionally by recruiting CCR4/Twin of deadenylation complex. Thus, we propose that an RBP complex regulates the dynamic APA profile to promote the mitosis-to-meiosis transition.
在有性生殖的生物中，配子是通过减数分裂产生的，随后是有限的有丝分裂扩增。然而，将细胞从有丝分裂切换到减数分裂周期的内在程序尚不清楚。交替多聚腺苷酸化（APA）是一种高度保守的基因调控方式，是通过 RNA 3'加工机制来实现的，以产生不同的 3'UTR 图谱。在果蝇精子发生过程中，我们观察到有丝分裂和减数分裂细胞之间转录组范围的 3'UTR 存在明显的差异。在停滞在有丝分裂中的突变体生殖细胞中，数百个基因的 3'UTR 持续移位。值得注意的是，改变多个 3'加工因子的水平会破坏生殖细胞向减数分裂的进展，表明 APA 在这个转变中发挥着积极的作用。一种 RNA 结合蛋白（RBP）Tut 可以直接结合 3'UTR 上的 3'加工因子，当 Tut 包含的复合物存在时，这些因子的表达被抑制。此外，我们证明这个 RBP 复合物可以通过招募 CCR4/Twin 去腺苷酸化复合物来进行转录后抑制。因此，我们提出一个 RBP 复合物可以调节动态 APA 图谱，以促进有丝分裂到减数分裂的转变。
