An E2 enzyme Ubc11 is required for ubiquitination of Slp1/Cdc20 and spindle checkpoint silencing in fission yeast

Horikoshi, Yasunori; Habu, Toshiyuki; Matsumoto, Tomohiro

doi:10.4161/cc.23946

Cited by 7 publications

(4 citation statements)

References 72 publications

(76 reference statements)

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“…We determined protein half‐lives by translation shut‐off using cycloheximide, followed by immunoblotting. The half‐lives of Mad1, Mad2, and Mad3 were in the range of many hours, considerably longer than the typical S. pombe cell cycle of 2.5 h (Fig 2E ; Appendix Fig S2E ) and broadly consistent with previous data (Sczaniecka et al , 2008 ; Horikoshi et al , 2013 ; Christiano et al , 2014 ). This large difference in mRNA and protein half‐lives explains the low cell‐to‐cell variability in protein concentration despite the considerable variation in mRNA numbers (Fig 2C ).…”

Section: Resultssupporting

confidence: 90%

Mitotic checkpoint gene expression is tuned by codon usage bias

et al. 2022

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The mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Correct functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about the regulation of SAC gene expression. Here, we show in the fission yeast Schizosaccharomyces pombe that a combination of short mRNA half-lives and long protein half-lives supports stable SAC protein levels. For the SAC genes mad2 + and mad3 + , their short mRNA half-lives are caused, in part, by a high frequency of nonoptimal codons. In contrast, mad1 + mRNA has a short half-life despite a higher frequency of optimal codons, and despite the lack of known RNAdestabilizing motifs. Hence, different SAC genes employ different strategies of expression. We further show that Mad1 homodimers form co-translationally, which may necessitate a certain codon usage pattern. Taken together, we propose that the codon usage of SAC genes is fine-tuned to ensure proper SAC function. Our work shines light on gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.

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Section: Resultssupporting

confidence: 90%

Mitotic checkpoint gene expression is tuned by codon usage bias

et al. 2022

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“…The half-lives of Mad1, Mad2 and Mad3 were in the range of many hours, considerably longer than the typical S. pombe cell cycle of 2.5 hours (Fig. 2E; S3E) and broadly consistent with previous data (Christiano et al, 2014;Horikoshi et al, 2013;Sczaniecka et al, 2008). This large difference in mRNA and protein half-lives explains the low cell-to-cell variability in protein concentration despite the considerable variation in mRNA numbers (Fig.…”

Section: Low Protein Noise Can Be Explained Through Long Protein and Short Mrna Half-livessupporting

confidence: 89%

Mitotic checkpoint gene expression is tuned by coding sequences

Esposito

et al. 2021

Preprint

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The mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Proper functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about SAC gene expression. Here, we show in fission yeast (S. pombe) that a combination of short mRNA half-lives and long protein half-lives supports stable SAC protein levels. For the SAC genes mad2+ and mad3+, their short mRNA half-lives depend on a high frequency of non-optimal codons and mRNA destabilization mediated through the RNA helicase Ste13 (S.c. Dhh1). In contrast, mad1+ mRNA half-life is short despite a relatively high frequency of optimal codons and despite the lack of known destabilizing motifs in its mRNA. Hence, although they are functionally related, different SAC genes employ different strategies of expression. Taken together, we propose that the codon usage of SAC genes is fine-tuned for proper SAC function. Our work shines light on the gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.

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“…Furthermore, inactivation of the SAC allows the dissociation of Cdc20 from this protein complex and its binding to APC/C (10, 44). It has been shown that Ube2C and ‐S are essential for the dissociation of Cdc20 from Mad2 and BubR1 (28, 41, 45). Thus, it is likely that the inability of the APC/C to bind its coactivator Cdc20 in the absence of Ube2C or ‐S contributes to the phenotype of hindered meiotic division.…”

Section: Discussionmentioning

confidence: 99%

Appropriate expression of Ube2C and Ube2S controls the progression of the first meiotic division

et al. 2015

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Timely degradation of protein regulators of the cell cycle is essential for the completion of cell division. This degradation is promoted by the E3 anaphase-promoting complex/cyclosome (APC/C) and mediated by the E2 ubiquitin-conjugating enzymes (Ube2s). Unlike the ample information gathered regarding the meiotic E3 APC/C, the E2s participating in this cell division have never been studied. We identified Ube2C, -S, and -D3 as the E2 enzymes that regulate APC/C activity during meiosis of mouse oocytes. Their depletion reduces the levels of the first meiotic cytokinesis by 50%, and their overexpression doubles and accelerates its completion (50% as compared with 4% at 11 h). We also demonstrated that these E2s take part in ensuring appropriate spindle formation. It is noteworthy that high levels of Ube2C bring about the resumption of the first meiotic division, regardless of the formation of the spindle, overriding the spindle assembly checkpoint. Thus, alongside their canonical function in protein degradation, Ube2C and -S also control the extrusion of the first polar body. Overall, our study characterizes new regulators and unveils the novel roles they play during the meiotic division. These findings shed light on faithful chromosome segregation in oocytes and may contribute to better understanding of aneuploidy and its consequent genetic malformations.

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An E2 enzyme Ubc11 is required for ubiquitination of Slp1/Cdc20 and spindle checkpoint silencing in fission yeast

Cited by 7 publications

References 72 publications

Mitotic checkpoint gene expression is tuned by codon usage bias

Mitotic checkpoint gene expression is tuned by codon usage bias

Mitotic checkpoint gene expression is tuned by coding sequences

Appropriate expression of Ube2C and Ube2S controls the progression of the first meiotic division

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