DAZL
Deleted in azoospermia-like (DAZ homolog) (DAZ-like autosomal) (Deleted in azoospermia-like 1) (SPGY-like-autosomal) [DAZH] [DAZL1] [DAZLA] [SPGYLA]
Publications[править]
The RNA binding protein DAZL is essential for gametogenesis, but its direct in vivo functions, RNA targets, and the molecular basis for germ cell loss in Dazl-null mice are unknown. Here, we mapped transcriptome-wide DAZL-RNA interactions in vivo, revealing DAZL binding to thousands of mRNAs via polyA-proximal 3' UTR interactions. In parallel, fluorescence-activated cell sorting and RNA-seq identified mRNAs sensitive to DAZL deletion in male germ cells. Despite binding a broad set of mRNAs, integrative analyses indicate that DAZL post-transcriptionally controls only a subset of its mRNA targets, namely those corresponding to a network of genes that are critical for germ cell proliferation and survival. In addition, we provide evidence that polyA sequences have key roles in specifying DAZL-RNA interactions across the transcriptome. Our results reveal a mechanism for DAZL-RNA binding and illustrate that DAZL functions as a master regulator of a post-transcriptional mRNA program essential for germ cell survival.
MeSH Terms
- 3' Untranslated Regions
- 5' Untranslated Regions
- Aging
- Animals
- Base Sequence
- Binding Sites
- Cell Cycle
- Cell Survival
- Female
- Gene Expression Regulation
- Gene Regulatory Networks
- Germ Cells
- Male
- Mice, Inbred C57BL
- Poly A
- Protein Binding
- RNA, Messenger
- RNA-Binding Proteins
- Testis
- Transcription, Genetic
- Transcriptome
Keywords
- 3′ UTR
- DAZL
- RNA binding protein
- RNA networks
- germ cell survival
- post-transcriptional regulation
- spermatogenesis
Female germline or oogonial stem cells transiently residing in fetal ovaries are analogous to the spermatogonial stem cells or germline stem cells (GSCs) in adult testes where GSCs and meiosis continuously renew. Oocytes can be generated in vitro from embryonic stem cells and induced pluripotent stem cells, but the existence of GSCs and neo-oogenesis in adult mammalian ovaries is less clear. Preliminary findings of GSCs and neo-oogenesis in mice and humans have not been consistently reproducible. Monkeys provide the most relevant model of human ovarian biology. We searched for GSCs and neo-meiosis in ovaries of adult monkeys at various ages, and compared them with GSCs from adult monkey testis, which are characterized by cytoplasmic staining for the germ cell marker DAZL and nuclear expression of the proliferative markers PCNA and KI67, and pluripotency-associated genes LIN28 and SOX2, and lack of nuclear LAMIN A, a marker for cell differentiation. Early meiocytes undergo homologous pairing at prophase I distinguished by synaptonemal complex lateral filaments with telomere perinuclear distribution. By exhaustive searching using comprehensive experimental approaches, we show that proliferative GSCs and neo-meiocytes by these specific criteria were undetectable in adult mouse and monkey ovaries. However, we found proliferative nongermline somatic stem cells that do not express LAMIN A and germ cell markers in the adult ovaries, notably in the cortex and granulosa cells of growing follicles. These data support the paradigm that adult ovaries do not undergo germ cell renewal, which may contribute significantly to ovarian senescence that occurs with age.
MeSH Terms
- Adult Stem Cells
- Animals
- Cell Differentiation
- Cellular Senescence
- Female
- Haplorhini
- Male
- Meiosis
- Mice
- Oogenesis
- Ovarian Follicle
- Ovary
Keywords
- Aging
- Germline stem cells
- Meiosis
- Monkey
- Oogenesis
- Ovary