|
General Comment |
NCBI Summary:
This gene encodes a nuclear protein which is involved in cell-cycle regulation. The encoded protein is a ubiquitin-ligase capable of ubiquinating PCNP (PEST-containing nuclear protein), and together they may play a role in tumorigenesis. The encoded protein contains an NIRF_N domain, a PHD finger, a set- and ring-associated (SRA) domain, and a RING finger domain and several of these domains have been shown to be essential for the regulation of cell proliferation. This protein may also have a role in intranuclear degradation of polyglutamine aggregates. Alternative splicing results in multiple transcript variants some of which are non-protein coding. [provided by RefSeq, Feb 2012]
|
|
Comment |
The dormant and the fully competent oocyte: comparing the transcriptome of human oocytes from primordial follicles and in metaphase ii. Grndahl ML et al. Oocytes become enclosed in primordial follicles during fetal life and remain there dormant until activation followed by growth and meiotic resumption. Current knowledge about the molecular pathways involved in oogenesis is incomplete. This study identifies the specific transcriptome of the human oocyte in the quiescent state and at the pinnacle of maturity at ovulation. In silico bioinformatic comparisons were performed between transcriptome of human oocytes from dormant primordial follicles and that of human metaphase II (MII) oocytes and granulosa cells and unique gene expression profiles were identified as well as functional and pathway enrichments associated with the oocytes from the two developmental hallmarks. A total of 729 genes were highly enriched in oocytes from primodial folllicles and 1456 genes were highly enriched in MII oocytes (>10 fold, p<0.001) representing functional categories such as cell cycle regulation, DNA protection and epigenetics, with representative genes validated by qPCR analysis. Dominating canonical pathways in the oocytes from primordial follicles were androgen, estrogen receptor, glucocortocoid receptor and PI3 K/AKT signaling (p<0.001). In the MII, mitotic roles of polo-like kinases, estrogen receptor, JAK/Stat signaling (p<0.001) and the ERK/MAPK (p<0.01) signaling were enriched. Some of the highly differentially expressed genes were completely new in human reproduction (CDR1, TLC1A, UHRF2) while other genes (ABO, FOLR1 (folate receptor), CHRNA3 (nicotine receptor)) may relate to clinical observations as diverse as premature ovarian failure, folic acid deficiency and smoking affecting female fertility. The in silico analysis identified novel reproduction associated genes and highlighted molecular mechanisms and pathways associated to the unique functions of the human oocyte in its two extremes of the folliculogenesis. The data provides a fundamental basis for future functional studies in regulation of human oogenesis.
|