IndraLab

Statements

RLIM binds USP26. 28 / 28
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"Our results thus far indicated that the RNF12-USP26 axis specifically operates in the testes and promotes the expression of genes associated with gametogenesis."
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"Finally, we investigated whether the RNF12-USP26 axis is dysregulated in human disease."
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"Furthermore, this RNF12-USP26 axis was disrupted by RLIM and USP26 variants found in TOKAS and infertility patients, respectively."
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"Finally, we showed that the RNF12-USP26 axis operated specifically in the testes and was disrupted in human genetic disorders associated with genital abnormalities and/or infertility."
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"These data suggest that the RNF12-USP26 axis may function to promote the expression of genes that are required for gametogenesis and germ cell development, consistent with a functional role for the RNF12-USP26 axis in the testes."
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"Notably, Usp26 expression was largely dependent on RNF12 in these experiments ( xref ), confirming that the RNF12-USP26 axis is operational in the context of PGCLC differentiation."
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"This RNF12-USP26 amplification loop specifically operated in testes and promoted efficient expression of genes that were associated with gametogenesis and germ cell differentiation in vitro, including Dazl ( xref ), Usp9y ( xref ), and Dppa3 ( xref )."
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"We therefore hypothesized that USP26 variants identified from azoospermia patients may also lead to deregulation of the RNF12-USP26 axis and gametogenesis gene expression."
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"To determine the impact of a TOKAS-associated RNF12 variant on the regulation and function of the RNF12-USP26 axis, we took advantage of knock-in mESCs harboring the mouse equivalent of the human RNF12 R599C variant identified from a TOKAS patient kindred (RNF12 R575C-KI) ( xref )."
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"Our data therefore demonstrate that a RNF12 TOKAS variant disrupts expression of Usp26 and other gametogenesis genes, suggesting that the RNF12-USP26 axis is likely impaired in patients harboring a disease-causing variant of RNF12."
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"Finally, we showed that the RNF12-USP26 axis was disrupted by RLIM variants from TOKAS patients, whereas RNF12 stabilization and downstream transcriptional regulation was disrupted by USP26 gene variants identified from azoospermia patients."
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"The RNF12-USP26 signaling axis operates specifically in the testes."
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"These data suggest that RNF12 and USP26 may form a complex in mESCs."
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"Therefore, further research is required to determine the specific function of RNF12-USP26 in gametogenesis in vivo."
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"Collectively, our results thus far reveal that Usp26 is transcriptionally induced by RNF12-dependent degradation of REX1, leading to the formation of a RNF12-USP26 complex that stabilizes RNF12."
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"We next sought to determine the function of RNF12-USP26 complex formation."
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"We next investigated the physiological function of the RNF12-USP26 signaling axis."
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"Taken together, our data indicate that the RNF12-USP26 axis promotes gametogenesis gene expression, and this is functionally disrupted by RLIM and USP26 variants associated with TOKAS and azoospermia, respectively."
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"To explore the possibility that RNF12-USP26 signaling may contribute to spermatogenesis, we first sought to confirm the tissue distribution of RNF12 and USP26."
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"An RNF12-USP26 amplification loop drives germ cell specification and is disrupted by disease-associated mutations."
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"However, the specific role of the RNF12-USP26 axis in gametogenesis and fertility in vivo is yet to be determined."
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"These data confirm that the RNF12-USP26 signaling axis operates specifically in the mouse testes, raising the possibility that it may play an important function in this context."
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"RNF12-USP26 complexing inhibited RNF12 autoubiquitylation, thereby stabilizing RNF12 to establish a feed-forward loop that amplified RNF12-dependent developmental gene expression."
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"In order to identify potential molecular functions of the RNF12-USP26 axis that may be relevant to the biology of male reproduction and fertility, we analyzed our previously reported RNA-SEQ dataset for RNF12-dependent mRNAs ( xref )."
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"We showed that the RNF12-USP26 axis operated specifically in mouse testes and was required for the expression of gametogenesis genes and for germ cell differentiation in vitro."
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"Mechanistically, the RNF12-mediated ubiquitylation and resulting degradation of the transcriptional repressor REX1 derepressed Usp26 expression, which drove a biochemical interaction between USP26 and RNF12."
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"Disrupted RNF12-USP26 signaling contributes to Tonne-Kalscheuer Syndrome (TOKAS) and azoospermia."
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"RNF12 relieved REX1-mediated repression of Usp26 , leading to an increase in USP26 abundance and the formation of RNF12-USP26 complexes."
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