The Drosophila 'Aurora' and S. cerevisiae Ipl1 protein kinases are involved in mitotic events such as centrosome separation and chromosome segregation. By screening a human placenta library with Xenopus Eg2 (an Aurora/Ipl1-related kinase) cDNA, Bernard et al. (1998) isolated a partial STK13 cDNA. They obtained a full-length cDNA using RACE on testis mRNA. The catalytic domain of the predicted 275-amino acid protein shares 80% and 68% identity with those of AURORA2 (603072) and AIK (602687), respectively.
NCBI Summary:
This gene encodes a member of the Aurora subfamily of serine/threonine protein kinases. The encoded protein is a chromosomal passenger protein that forms complexes with Aurora-B and inner centromere proteins and may play a role in organizing microtubules in relation to centrosome/spindle function during mitosis. This gene is overexpressed in several cancer cell lines, suggesting an involvement in oncogenic signal transduction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]
General function
RNA processing, Enzyme
Comment
Selective Disruption of Aurora C Kinase Reveals Distinct Functions from Aurora B Kinase during Meiosis in Mouse Oocytes. Balboula AZ 2014 et al.
Aurora B kinase (AURKB) is the catalytic subunit of the chromosomal passenger complex (CPC), an essential regulator of chromosome segregation. In mitosis, the CPC is required to regulate kinetochore microtubule (K-MT) attachments, the spindle assembly checkpoint, and cytokinesis. Germ cells express an AURKB homolog, AURKC, which can also function in the CPC. Separation of AURKB and AURKC function during meiosis in oocytes by conventional approaches has not been successful. Therefore, the meiotic function of AURKC is still not fully understood. Here, we describe an ATP-binding-pocket-AURKC mutant, that when expressed in mouse oocytes specifically perturbs AURKC-CPC and not AURKB-CPC function. Using this mutant we show for the first time that AURKC has functions that do not overlap with AURKB. These functions include regulating localized CPC activity and regulating chromosome alignment and K-MT attachments at metaphase of meiosis I (Met I). We find that AURKC-CPC is not the sole CPC complex that regulates the spindle assembly checkpoint in meiosis, and as a result most AURKC-perturbed oocytes arrest at Met I. A small subset of oocytes do proceed through cytokinesis normally, suggesting that AURKC-CPC is not the sole CPC complex during telophase I. But, the resulting eggs are aneuploid, indicating that AURKC is a critical regulator of meiotic chromosome segregation in female gametes. Taken together, these data suggest that mammalian oocytes contain AURKC to efficiently execute meiosis I and ensure high-quality eggs necessary for sexual reproduction.
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Cellular localization
Cytoplasmic
Comment
Ovarian function
Oocyte maturation, Early embryo development
Comment
Maternal RNA regulates Aurora C kinase during mouse oocyte maturation in a translation-independent fashion. Balboula AZ et al. (2017) During oocyte meiotic maturation, Aurora kinase C (AURKC) is required to accomplish many critical functions including destabilizing erroneous kinetochore-microtubule attachments (K-MT) and regulating bipolar spindle assembly. How localized activity of AURKC is regulated in mammalian oocytes, however, is not fully understood. Female gametes from many species, including mouse, contain stores of maternal transcripts that are required for downstream developmental events. We show here that depletion of maternal RNA in mouse oocytes resulted in impaired meiotic progression, increased incidence of chromosome misalignment and abnormal spindle formation at metaphase I (Met I), and cytokinesis defects. Importantly, depletion of maternal RNA perturbed the localization and activity of AURKC within the chromosomal passenger complex (CPC). These perturbations were not observed when translation was inhibited by cycloheximide (CHX) treatment. These results demonstrate a translation-independent function of maternal RNA to regulate AURKC-CPC function in mouse oocytes.//////////////////
Aurora-C Kinase Deficiency Causes Cytokinesis Failure in Meiosis I and Production of Large Polyploid Oocytes in Mouse. Yang KT et al. Monitoring Editor: Stephen Doxsey We previously isolated Aurora-C/Aie1 in a screen for kinases expressed in mouse sperm and eggs. Here, we show the localization of endogenous Aurora-C and examine its roles during female mouse meiosis. Aurora-C was detected at the centromeres and along the chromosome arms in prometaphase I/metaphase I and was concentrated at centromeres at metaphase II, in which Aurora-C was also phosphorylated at Thr171. During the anaphase I/telophase I transition, Aurora-C was dephosphorylated and relocalized to the midzone and midbody. Microinjection of the kinase-deficient Aurora-C (AurC-KD) mRNA into mouse oocytes significantly inhibited Aurora-C activity and caused multiple defects, including chromosome misalignment, abnormal kinetochore-microtubule attachment, premature chromosome segregation, and cytokinesis failure in meiosis I. Furthermore, AurC-KD also reduced Aurora-C and histone H3 phosphorylation, and inhibited kinetochore localization of Bub1 and BubR1. Similar effects were also observed in the oocytes injected with INCNEP-delIN mRNAs, in which the Aurora-C binding motif was removed. The most dramatic effect observed in AurC-KD injected oocytes is cytokinesis failure in meiosis I, resulting in producing large polyploid oocytes, a pattern similar to Aurora-C deficiency human spermatozoa. Surprisingly, we detected no Aurora-B protein in mouse oocytes. We propose that Aurora-C, but not Aurora-B, plays essential roles in female mouse meiosis.
Full-grown Xenopus oocytes arrest at the G2/M border of meiosis I. Progesterone breaks this arrest, leading to the resumption of the meiotic cell cycles and maturation of the oocyte into a fertilizable egg. In these oocytes, progesterone interacts with an unidentified surface-associated receptor, which induces a nontranscriptional signaling pathway that stimulates the translation of dormant c-mos mRNA. The translational recruitment of c-mos and several other mRNAs is regulated by cytoplasmic polyadenylation, a process that requires two 3-prime untranslated regions, the cytoplasmic polyadenylation element (CPE) and the polyadenylation hexanucleotide AAUAAA. Mendez et al. (2000) demonstrated that an early site-specific phosphorylation of CPEB (the CPE binding factor) is essential for the polyadenylation of c-mos mRNA and its subsequent translation, and for oocyte maturation. In addition, they showed that this selective, early phosphorylation of CPEB is catalyzed by Eg2.
A role for Aurora C in the chromosomal passenger complex during human preimplantation embryo development. Avo Santos M et al. BACKGROUND Human embryos generated by IVF demonstrate a high incidence of chromosomal segregation errors during the cleavage divisions. To analyse underlying molecular mechanisms, we investigated the behaviour of the chromosomal passenger complex (CPC) in human oocytes and embryos. This important mitotic regulatory complex comprises the inner centromere protein (INCENP), survivin, borealin and Aurora B, or the meiotic kinase Aurora C. METHODS We analysed mRNA expression by quantitative RT-PCR of all CPC members in human oocytes, tripronuclear (3PN) zygotes, 2-cell and 4-cell embryos developed from 3PN zygotes, plus good-quality cryopreserved 8-cell, morula and blastocyst stage embryos. Protein expression and localization of CPC members were investigated by immunofluorescence in oocytes and embryos arrested at prometaphase. Histone H3S10 phosphorylation was investigated as an indicator of a functional CPC. RESULTS INCENP, survivin and borealin were detected at the inner centromere of prometaphase chromosomes in all stages investigated. Whereas Aurora B and C are both present in oocytes, Aurora C becomes the most prominent kinase in the CPC during the first three embryonic cell cycles. Moreover, Aurora C mRNA was up-regulated with Aurora B after activation of the embryonic genome and both proteins were detected in early Day 4 embryos. Subsequently, only Aurora B was detected in blastocysts. CONCLUSIONS In contrast to somatic cells, our results point to a specific role for Aurora C in the CPC during human preimplantation embryo development. Although, the presence of Aurora C in itself may not explain the high chromosome segregation error rate, the data presented here provide novel information regarding possible mechanisms.
Expression regulated by
Comment
Ovarian localization
Oocyte
Comment
Expression and characterization of three Aurora kinase C splice variants found in human oocytes. Fellmeth JE et al. (2015) Chromosome segregation is an extensively choreographed process yet errors still occur frequently in female meiosis, leading to implantation failure, miscarriage or offspring with developmental disorders. Aurora kinase C (AURKC) is a component of the chromosome passenger complex and is highly expressed in gametes. Studies in mouse oocytes indicate that AURKC is required to regulate chromosome segregation during meiosis I (MI); however, little is known about the functional significance of AURKC in human oocytes. Three splice variants of AURKC exist in testis tissue. To determine which splice variants human oocytes express, we performed quantitative real time PCR using single oocytes and found expression of all three variants. To evaluate the functional differences between the variants, we created GFP-tagged constructs of each variant to express in oocytes from Aurkc(-/-) mice. By quantifying metaphase chromosome alignment, cell cycle progression, phosphorylation of INCENP, and microtubule attachments to kinetochores, we found that AURKC_v1 was the most capable of the variants at supporting metaphase I chromosome segregation. AURKC_v3 localized to chromosomes properly and supported cell cycle progression to metaphase II, but its inability to correct erroneous microtubule attachments to kinetochores meant that chromosome segregation was not as accurate compared to that caused by the other three variants. Finally when we expressed the three variants simultaneously, error correction was more robust than when they were expressed on their own. Therefore, oocytes express three variants of AURKC that are not functionally equivalent in supporting meiosis, but fully complement meiosis when expressed simultaneously.//////////////////
The human cumulus-oocyte complex gene-expression profile. Assou S et al. BACKGROUND: The understanding of the mechanisms regulating human oocyte maturation is still rudimentary. We have identified transcripts differentially expressed between immature and mature oocytes and cumulus cells.
Follicle stages
Antral, Preovulatory
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment: Maternally recruited Aurora C kinase is more stable than Aurora B to support mouse oocyte maturation and early development. Schindler K et al. Aurora kinases are highly conserved, essential regulators of cell division. Two Aurora kinase isoforms, A and B (AURKA and AURKB), are expressed ubiquitously in mammals, whereas a third isoform, Aurora C (AURKC), is largely restricted to germ cells. Because AURKC is very similar to AURKB, based on sequence and functional analyses, why germ cells express AURKC is unclear. We report that Aurkc(-/-) females are subfertile, and that AURKB function declines as development progresses based on increasing severity of cytokinesis failure and arrested embryonic development. Furthermore, we find that neither Aurkb nor Aurkc is expressed after the one-cell stage, and that AURKC is more stable during maturation than AURKB using fluorescently tagged reporter proteins. In addition, Aurkc mRNA is recruited during maturation. Because maturation occurs in the absence of transcription, posttranscriptional regulation of Aurkc mRNA, coupled with the greater stability of AURKC protein, provides a means to ensure sufficient Aurora kinase activity, despite loss of AURKB, to support both meiotic and early embryonic cell divisions. These findings suggest a model for the presence of AURKC in oocytes: that AURKC compensates for loss of AURKB through differences in both message recruitment and protein stability.