Heightened protein-translation activities in mammalian cells and the disease/treatment implications.

Heightened protein-translation activities in mammalian cells and the disease/treatment implications.
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哺乳动物细胞中蛋白质翻译活性的增强及其疾病/治疗的影响

DOI:
10.1093/nsr/nwaa066
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发表时间:
2020-12
影响因子:
20.6
通讯作者:
Wen H
Wen H
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wu CI;Wen H

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细胞分裂后,新的细胞必须及时合成所有必要的细胞成分,以便进行下一次分裂。单元格将其内容加倍所需的时间有一个下限。对于哺乳动物细胞来说,这一下限可能是20小时左右,因为人工选择分裂更快的细胞并没有推动细胞系在加倍时间内低于这一“障碍”。偶尔出现的例外情况是那些似乎在“证明规则”的人。例如,酵母细胞可以每1.5小时分裂一次[1,2],后生动物的细胞分裂速度最快的可能是果蝇的胚胎细胞,每周期5分钟[3]。因此,至少对于真核细胞来说,限速步骤并不是DNA的复制。这一速率限制步骤对细胞生物学和许多疾病都是重要的(尽管重点已经转移到基于突变的方法,如基因定位和疫苗开发)。对于沿着中央教条的成分,每个细胞中每个基因只有两个拷贝,哺乳动物细胞中∼的中位数被报道为17。引人注目的是,蛋白质的中位数为5万[4]。由于从信使核糖核酸到蛋白质的数量增加了3000倍,而DNA和信使核糖核酸含量的增加分别只有2倍和17倍,因此限制速度的步骤可能是蛋白质合成[5]。事实上,蛋白质翻译是一个耗能很高的过程,消耗的能量是哺乳动物细胞所用能量的30%。
After cells divide, the new cells have to synthesize all the necessary cellular components in time for the next division. There is a lower bound of time required for cells to double their contents. For mammalian cells, this lower bound may be around 20 hours, as artificial selection for faster-dividing cells has not pushed cell lines to go below this ‘barrier’in doubling time. The occasional exceptions are those that appear to ‘prove the rule’. For example, yeast cells can divide once every 1.5 hours [1, 2], and the fastest rate of cell divisions in metazoans may be that of the embryonic cells of Drosophila, at5 minutes per cycle [3]. Thus, at least for eukaryotic cells, the rate-limiting step is not the replication of DNA. This rate-limiting step is central to cell biology as well as many diseases (although emphasis has been shifting to mutation-based approaches such as genetargeting and vaccine development). For the components along the central dogma, each cell has only two copies of the DNA for every gene and the median number of mRNAs in mammalian cells has been reported to be∼ 17. Strikingly, the median number of proteins is 50 000 [4]. As there is a 3000-fold increase in quantity from mRNA to protein, whereas the increases in DNA and mRNA content are only 2-fold and 17-fold, respectively, the rate-limiting step is likely to be protein synthesis [5]. Indeed, protein translation is an energy-demanding process [6], consuming 30% of the energy used by mammalian cells.
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