E3 ubiquitin-protein ligase that cooperates with the microRNAs (miRNAs) machinery and promotes embryonic stem cells proliferation and maintenance (PubMed:19898466). Binds to miRNAs and associates with AGO2, participating in post-transcriptional repression of transcripts such as CDKN1A. Facilitates the G1-S transition to promote rapid embryonic stem cell self-renewal by repressing CDKN1A expression (PubMed:22735451). In addition, participates in post-transcriptional mRNA repression in a miRNA independent mechanism (PubMed:23125361). Required to maintain proliferation and prevent premature differentiation of neural progenitor cells during early neural development: positively regulates FGF signaling by controlling the stability of SHCBP1 (PubMed:22735451). Specific regulator of miRNA biogenesis. miRNA Binds MIR29A hairpin and postranscriptionally modulates MIR29A levels, which indirectly regulates TET proteins expression (By similarity). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Interacts (via NHL repeats) with AGO2; the interaction increases in presence of RNA (PubMed:19898466, PubMed:22508726, PubMed:22735451). Interacts with HSP90AA1. Interacts (via NHL repeats) with MOV10, PABPC1, PUM1, PUM2, STAU2, XRN1 and XRN2 in an RNA-dependent manner (By similarity). Interacts with SHCBP1; leading to enhance its stability (PubMed:22508726). Highly expressed in undifferentiated embryonic stem cells (ESCs). Expressed in the epiblast and in interfollicular epidermal stem cells during early development. Also expressed in male germ cells and in the reproductive tract. Highly expressed in neuroepithelial cells, and its expression declines as neurogenesis proceeds (at protein level). Expressed in ependymal cells of the brain (PubMed:25883935). Expression is first detected at 8.5 dpc, increases to highest levels at 14.5 dpc and remains elevated through the newborn stage. Expressed in developing limb buds and tail buds starting from 9.5 dpc. At 9.5 dpc, expression is prominent in the entire embryo, with the exception of the primordial cardiac sac. At 10.5 dpc, expression reduces to the neuroepithelium, branchial arches, spinal cord, somites, limb, and tail buds. At the onset of central nervous system development, the neuroepithelium shows a prominent staining between 9.5 dpc and 10.5 dpc. Thereafter, expression is unevenly distributed in a progressively thinner layer along the inner surface of the ventricle. Expression is intense at the bumps corresponding to the nascent limb buds around 10.5 dpc. Shortly thereafter, as the limb buds emerge from the body and expand, expression declines and is limited to the most distal surface at 12.5 dpc. At 13.5 dpc it is no longer possible to identify expression in either the developing nervous system, the limb or the tail buds. From postnatal day 10 (P10) to the adulthood, expressed in cells lining the wall of the four ventricles of the postnatal brain (PubMed:25883935). Negatively regulated by the microRNA (miRNA) let-7 which causes degradation of the mRNA encoding this protein. This requires a let-7 complementary site (LCS) in the 3'-UTR of the mRNA encoding this protein. The NHL domain, containing the 6 NHL repeats, is necessary and sufficient to target RNA but not to repress mRNA. The minimal region needed to execute repression consists of the coiled coil domain and the Filamin repeat. The RING-type domain is dispensable for mRNA repression. Autoubiquitinated. Embryonic lethality at 9.5 dpc, due to a neural tube closure defect in the anterior craniofacial region of the neural tube, corresponding to the forebrain/midbrain boundary. Reduced cell proliferation in the neuroepithelium. Belongs to the TRIM/RBCC family. Reported to mediate ubiquitination and subsequent degradation of AGO2 (PubMed:19898466). However, this result is subject to discussion and later reports suggest that, while it interacts with AGO2, it is not involved in AGO2 ubiquitination (PubMed:22508726, PubMed:22735451).