RDC complex executes a dynamic piRNA program during Drosophila spermatogenesis to safeguard male fertility
| Autor: | Alexei A. Aravin, Peiwei Chen, Yicheng Luo |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research Heredity Physiology QH426-470 Germline law.invention law Transcription (biology) Animal Cells Reproductive Physiology Spermatocytes Testis Medicine and Health Sciences Drosophila Proteins Testes Cell Cycle and Cell Division Genetics (clinical) Heterozygosity Chromosome Biology Genomics Cell biology Ovaries Meiosis Drosophila melanogaster Cell Processes Drosophila Anatomy Cellular Types Genital Anatomy Research Article endocrine system Piwi-interacting RNA Biology Genetics Gene silencing Animals Spermatogenesis Molecular Biology Gene Psychological repression Ecology Evolution Behavior and Systematics urogenital system Reproductive System Biology and Life Sciences Cell Biology Sperm Spermatogonia Germ Cells Suppressor Biogenesis |
| Zdroj: | PLoS Genetics PLoS Genetics, Vol 17, Iss 9, p e1009591 (2021) |
| Popis: | piRNAs are small non-coding RNAs that guide the silencing of transposons and other targets in animal gonads. In Drosophila female germline, many piRNA source loci dubbed “piRNA clusters” lack hallmarks of active genes and exploit an alternative path for transcription, which relies on the Rhino-Deadlock-Cutoff (RDC) complex. RDC was thought to be absent in testis, so it remains to date unknown how piRNA cluster transcription is regulated in the male germline. We found that components of RDC complex are expressed in male germ cells during early spermatogenesis, from germline stem cells (GSCs) to early spermatocytes. RDC is essential for expression of dual-strand piRNA clusters and transposon silencing in testis; however, it is dispensable for expression of Y-linked Suppressor of Stellate piRNAs and therefore Stellate silencing. Despite intact Stellate repression, males lacking RDC exhibited compromised fertility accompanied by germline DNA damage and GSC loss. Thus, piRNA-guided repression is essential for normal spermatogenesis beyond Stellate silencing. While RDC associates with multiple piRNA clusters in GSCs and early spermatogonia, its localization changes in later stages as RDC concentrates on a single X-linked locus, AT-chX. Dynamic RDC localization is paralleled by changes in piRNA cluster expression, indicating that RDC executes a fluid piRNA program during different stages of spermatogenesis. These results disprove the common belief that RDC is dispensable for piRNA biogenesis in testis and uncover the unexpected, sexually dimorphic and dynamic behavior of a core piRNA pathway machinery. Author summary Large fractions of eukaryotic genomes are occupied by mobile genetic elements called transposons. Active transposons can move in the genome causing DNA damage and mutations, while inactive copies can contribute to chromosome organization and regulation of gene expression. Host cells employ several mechanisms to discriminate transposons from other genes and repress transposon activities. In germ cells, a conserved class of short RNAs called Piwi-interacting (pi)RNAs recognize target RNAs in both the nucleus and cytoplasm and then guide transposon repression by preventing their transcription and destroying their RNAs. piRNAs are encoded in extended genomic regions dubbed piRNA clusters. Previously, composition and regulation of piRNA clusters were studied in the female germline of fruit flies, where a nuclear protein complex, the RDC complex, was shown to promote non-canonical transcription of these regions. However, RDC was believed to be dispensable in males. Here, we showed that RDC is essential for transposon repression in males, and males lacking RDC exhibit compromised fertility and loss of germ cells. We found that RDC binds multiple piRNA clusters in early germ cells but concentrates on a single locus at later stages. Our results indicate dynamic regulation of loci that produce piRNAs and, therefore, piRNA targets throughout spermatogenesis. |
| Databáze: | OpenAIRE |
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