On October 3th, 2018,Dr. Heng-Yu Fan’s group has published a paper in Cell Death and Differentiation（Impact factor 8.0）, which reported the key function of an evolutionarily conserved nucleolar protein DCAF13 in oogenesis.
Oocyte is the largest cell in all animals, ranging from 70 micrometers (rodents) to 2000 micrometers (amphibians) in diameter. Specific mechanisms are employed to support this magnificent oocyte growth in various animal groups. In insects, nurse cells transfer materials to oocytes through the cytoplasmic bridges that connect these two cell types. In fishes and amphibians, yolk proteins synthesized in the liver are transported to the oocytes by a blood circulation system. As an extreme example, the gene clusters that encode ribosomal RNAs (rRNAs) are amplified in fast-growing Xenopus oocytes to facilitate rRNA synthesis. Nevertheless, similar mechanisms do not exist in mammalian oogenesis. The genes and pathways that support mammalian oocyte growth after primordial-follicle awakening are poorly understood.During mammalian oocyte growth, chromatin configuration transition from the nonsurrounded nucleolus (NSN) to surrounded nucleolus (SN) type plays a key role in the regulation of gene expression and in acquisition of meiotic and developmental competence by the oocyte. Nonetheless, the mechanism underlying chromatin configuration maturation in oocytes is poorly understood.
In this study, people from Fan group show that nucleolar protein DCAF13 is an important component of the ribosomal RNA (rRNA)-processing complex and is essential for oocyte NSN�SN transition in mice. A conditional knockout of Dcaf13 in oocytes led to the arrest of oocyte development in the NSN configuration, follicular atresia, premature ovarian failure, and female sterility. The DCAF13 deficiency resulted in pre-rRNA accumulation in oocytes, whereas the total mRNA level was not altered. Further exploration showed that DCAF13 participated in the 18S rRNA processing in growing oocytes. The lack of 18S rRNA because of DCAF13 deletion caused a ribosome assembly disorder and then reduced global protein synthesis. DCAF13 interacted with a protein of the core box C/D ribonucleoprotein, fibrillarin, i.e., a factor of early pre-rRNA processing. When fibrillarin was knocked down in oocytes from primary follicles, the follicle development was inhibited as well, indicating that an rRNA processing defect in the oocyte indeed stunts chromatin configuration transition and follicle development. Taken together, these results elucidated the in vivo function of novel nucleolar protein DCAF13 in maintaining mammalian oogenesis.
Summary of DCAF13 function in rRNA processing and oocyte and follicle development
A: Duringfollicle development, growing oocytes undergo a translationally active growing phase in which necessary protein are synthesized. DCAF13 deletion in oocytes compromised nucleolus NSN-SN configuration transition and caused global down-regulation of protein accumulation, whichcause follicular development arrest in early secondary follicles.
B: In the nucleolus,the 47S ribosomal precursor RNA (pre-rRNA) is cleaved to form the mature 28S, 18S and 5.8S rRNAs. During this maturation process, the pre-rRNA and its processing intermediates undergo numerous post-transcriptional modifications, which are guided and catalyzed by small nucleolar RNAs (snoRNPs) and their interacting proteins including NOP56and fibrillarin.DCAF13 has strong interaction with NOP56and fibrillarin which are associated with box C/D U3 snoRNA to participate the processing of18S rRNAprocessing. DCAF13 ensure enough mature 18S rRNA in cytoplasm to assemble 40S subunit of ribosomes and regulates protein translation.
links: https://www.nature.com/articles/s41418-018-0203-7
