REGULATION OF HISTONE MESSENGER-RNA IN THE UNPERTURBED CELL-CYCLE - EVIDENCE SUGGESTING CONTROL AT 2 POSTTRANSCRIPTIONAL STEPS

REGULATION OF HISTONE MESSENGER-RNA IN THE UNPERTURBED CELL-CYCLE - EVIDENCE SUGGESTING CONTROL AT 2 POSTTRANSCRIPTIONAL STEPS
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DOI:
10.1128/mcb.11.5.2416
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发表时间:
1991-05-01
影响因子:
5.3
通讯作者:
MARZLUFF, WF
MARZLUFF, WF
中科院分区:
生物学2区
文献类型:
--
作者:
HARRIS, ME;BOHNI, R;MARZLUFF, WF

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当选择性分离的有丝分裂 CHO 细胞从有丝分裂经过 G1 并进入 S 期时,组蛋白 mRNA 水平增加 35 倍。 使用具有对转录或半衰期调节不敏感的组蛋白 3' 末端的外源基因,我们发现随着细胞从 G1 期进入 S 期,3' 加工受到调节。 G1 期和 S 期细胞中组蛋白 mRNA 的半衰期相似,通过放线菌素 D(放线菌素)抑制转录后测量,或通过蛋白质合成抑制剂放线菌酮稳定后间接测量。 总而言之,这些结果表明 G1 期和 S 期细胞之间组蛋白 mRNA 水平的变化必定是由于生物合成速率的增加、转录速率和加工效率的变化的组合。 在 G2 期,组蛋白 mRNA 浓度迅速下降 35 倍,我们的结果表明这主要是由于组蛋白 mRNA 的稳定性改变所致。 这些结果与组蛋白 mRNA 水平的细胞周期调节模型一致,其中对 RNA 3' 加工和转录的影响,而不是 mRNA 稳定性的改变,是 G1 期间维持低组蛋白 mRNA 水平的主要机制。
The levels of histone mRNA increase 35-fold as selectively detached mitotic CHO cells progress from mitosis through G1 and into S phase. Using an exogenous gene with a histone 3' end which is not sensitive to transcriptional or half-life regulation, we show that 3' processing is regulated as cells progress from G1 to S phase. The half-life of histone mRNA is similar in G1- and S-phase cells, as measured after inhibition of transcription by actinomycin D (dactinomycin) or indirectly after stabilization by the protein synthesis inhibitor cycloheximide. Taken together, these results suggest that the change in histone mRNA levels between G1- and S-phase cells must be due to an increase in the rate of biosynthesis, a combination of changes in transcription rate and processing efficiency. In G2 phase, there is a rapid 35-fold decrease in the histone mRNA concentration which our results suggest is due primarily to an altered stability of histone mRNA. These results are consistent with a model for cell cycle regulation of histone mRNA levels in which the effects on both RNA 3' processing and transcription, rather than alterations in mRNA stability, are the major mechanisms by which low histone mRNA levels are maintained during G1.