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mRNA localization to subcellular compartments has been reported across all kingdoms of life and it is generally believed to promote asymmetric protein synthesis and localization. In striking contrast to previous observations, we show that in S. cerevisiae the B-type cyclin CLB2 mRNA is localized and translated in the yeast bud, while the Clb2 protein, a key regulator of mitosis progression, is concentrated in the mother nucleus. Using single-molecule RNA imaging in fixed (smFISH) and living cells (MS2 system), we show that the CLB2 mRNA is transported to the yeast bud by the She2-She3 complex, via an mRNA ZIP-code situated in the coding sequence. In CLB2 mRNA localization mutants, Clb2 protein synthesis in the bud is decreased resulting in changes in cell cycle distribution and genetic instability. Altogether, we propose that CLB2 mRNA localization acts as a sensor for bud development to couple cell growth and cell cycle progression, revealing a novel function for mRNA localization.
Sarcomas are rare cancers with high heterogeneity in terms of type, location, and treatment. The health-related quality of life (HRQoL) of sarcoma patients has rarely been investigated and is the subject of this analysis. Adult sarcoma patients and survivors were assessed between September 2017 and February 2019 in 39 study centers in Germany using standardized, validated questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)). Associated factors were analyzed exploratively using multivariable linear regressions. Among 1113 patients, clinically important limitations and symptoms were most pronounced in emotional (63%, 95% CI 60–66%), physical (60%, 95% CI 57–62%), role functioning (51%, 95% CI 48–54%), and pain (56%, 95% CI 53–59%) and fatigue (51%, 95% CI 48–54%). HRQoL differed between tumor locations with lower extremities performing the worst and sarcoma types with bone sarcoma types being most affected. Additionally, female gender, higher age, lower socioeconomic status, recurrent disease, not being in retirement, comorbidities, and being in treatment were associated with lower HRQoL. Sarcoma patients are severely restricted in their HRQoL, especially in functioning scales. The heterogeneity of sarcomas with regard to type and location is reflected in HRQoL outcomes. During treatment and follow-up, close attention has to be paid to the reintegration of the patients into daily life as well as to their physical abilities and emotional distress.
Cyclin CLB2 mRNA localization and protein synthesis link cell cycle progression to bud growth
(2024)
Clb2 is a conserved mitotic B-type cyclin, the levels of which are finely controlled to drive progression through the cell cycle. While it is known that CLB2 transcription and Clb2 protein degradation are important for precise control of its expression, it remains unclear whether the synthesis of Clb2 is also regulated. To address whether and how Clb2 expression levels respond to cell growth changes and adapt cell cycle progression, we combined single-cell and single-molecule imaging methods to measure CLB2 mRNA and protein expression throughout the Saccharomyces cerevisiae cell cycle. We found that the CLB2 mRNA was efficiently localized to the yeast bud as soon as this compartment was formed, but strikingly the Clb2 protein accumulated in the mother nucleus. The CLB2 mRNA localization in the yeast bud by the She2-3 complex did not control protein localization but rather promoted CLB2 translation. Moreover, CLB2 mRNA bud localization and protein synthesis were coupled and dependent on a single secondary structure -a ZIP code-located in the coding sequence. In a CLB2 ZIP code mutant, mRNA localization was impaired and Clb2 protein synthesis decreased, resulting in changes in cell cycle distribution and increased size of daughter cells at birth. Finally, while in WT cells the Clb2 protein concentration followed bud growth, this relationship was impaired in the ZIP code mutant. We propose that S. cerevisiae couples the control of CLB2 mRNA bud localization and protein synthesis to coordinate cell growth and cell cycle progression. This mechanism extends our knowledge of CLB2 expression regulation, and constitutes a novel function for mRNA localization.