关键词: PIWI proteins RNA export nuclear export factor piRNA clusters transposon control

Mesh : Active Transport, Cell Nucleus / genetics Animals DNA Transposable Elements / genetics Drosophila / genetics metabolism Drosophila Proteins / genetics metabolism Intracellular Signaling Peptides and Proteins / genetics metabolism Nucleocytoplasmic Transport Proteins / genetics metabolism RNA Precursors / metabolism RNA, Small Interfering / metabolism RNA-Binding Proteins / genetics metabolism

来  源:   DOI:10.1101/gad.328690.119   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
The PIWI-interacting RNA (piRNA) pathway is a conserved small RNA-based immune system that protects animal germ cell genomes from the harmful effects of transposon mobilization. In Drosophila ovaries, most piRNAs originate from dual-strand clusters, which generate piRNAs from both genomic strands. Dual-strand clusters use noncanonical transcription mechanisms. Although transcribed by RNA polymerase II, cluster transcripts lack splicing signatures and poly(A) tails. mRNA processing is important for general mRNA export mediated by nuclear export factor 1 (Nxf1). Although UAP56, a component of the transcription and export complex, has been implicated in piRNA precursor export, it remains unknown how dual-strand cluster transcripts are specifically targeted for piRNA biogenesis by export from the nucleus to cytoplasmic processing centers. Here we report that dual-strand cluster transcript export requires CG13741/Bootlegger and the Drosophila nuclear export factor family protein Nxf3. Bootlegger is specifically recruited to piRNA clusters and in turn brings Nxf3. We found that Nxf3 specifically binds to piRNA precursors and is essential for their export to piRNA biogenesis sites, a process that is critical for germline transposon silencing. Our data shed light on how dual-strand clusters compensate for a lack of canonical features of mature mRNAs to be specifically exported via Nxf3, ensuring proper piRNA production.
摘要:
PIWI相互作用RNA(piRNA)途径是一种保守的基于小RNA的免疫系统,可保护动物生殖细胞基因组免受转座子动员的有害影响。在果蝇卵巢中,大多数piRNAs起源于双链簇,从两个基因组链产生piRNA。双链簇使用非规范转录机制。尽管由RNA聚合酶II转录,簇转录本缺乏剪接签名和poly(A)尾。mRNA加工重要由核输出因子1(Nxf1)介导的普通mRNA输出。虽然UAP56,转录和出口复合体的组成部分,与piRNA前体出口有关,目前尚不清楚双链簇转录物如何通过从细胞核输出到胞质加工中心来特异性靶向piRNA生物发生。在这里,我们报告了双链簇转录物的输出需要CG13741/Bootlegger和果蝇核输出因子家族蛋白Nxf3。Bootlegger被专门招募到piRNA簇,并反过来带来Nxf3。我们发现Nxf3特异性结合piRNA前体,并且对于它们向piRNA生物发生位点的输出是必不可少的,一个对于种系转座子沉默至关重要的过程。我们的数据揭示了双链簇如何补偿通过Nxf3特异性输出的成熟mRNA的规范特征的缺乏,确保适当的piRNA生产。
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