REGULATION OF C-MYC MESSENGER-RNA STABILITY INVITRO BY A LABILE DESTABILIZER WITH AN ESSENTIAL NUCLEIC-ACID COMPONENT
REGULATION OF C-MYC MESSENGER-RNA STABILITY INVITRO BY A LABILE DESTABILIZER WITH AN ESSENTIAL NUCLEIC-ACID COMPONENT
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DOI：
10.1128/mcb.9.5.1996
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发表时间：
1989-05-01
影响因子：
5.3
通讯作者：
ROSS, J
中科院分区：
文献类型：
--
作者：
BREWER, G;ROSS, J
当细胞改变其生长模式或分化时，一些mRNA的周转率变化一个数量级或更多。为了确定可能导致这种变异性的调节因子，我们研究了细胞溶质组分如何影响体外系统中mRNA的衰减。A 130，000倍。来自指数生长的红白血病细胞的胞质溶胶的2.5g上清液（S130）含有去稳定剂，与缺乏S130的反应相比，该去稳定剂加速了多核糖体结合的c-myc mRNA的衰减8倍或更多。去稳定剂是缺乏或不存在的S130的环己酰亚胺处理的细胞，表明它是不稳定的或被抑制时，翻译被阻断。它不是一般的RNA酶，因为它不影响δ的周转。珠蛋白，γ-珠蛋白或组蛋白mRNA，并且不使多聚体多腺苷酸化mRNA的主要部分不稳定。去稳定剂加速c-myc mRNA 3“区域的周转，以及随后mRNA体的3”至5“降解。它在体外通过温和加热和微球菌核酸酶失活，表明它含有核酸组分。c-myb mRNA在补充S130的体外反应中也不稳定。这些结果表明，一些mRNA的稳定性是由胞质因子，而不是与多聚核糖体。
The turnover rates of some mRNAs vary by an order of magnitude or more when cells change their growth pattern or differentiate. To identify regulatory factors that might be responsible for this variability, we investigated how cytosolic fractions affect mRNA decay in an in vitro system. A 130,000 .times. g supernatant (S130) from the cytosol of exponentially growing erythroleukemia cell contains a destabilizer that accelerates the decay of polysome-bound c-myc mRNA by eightfold or more compared with reactions lacking S130. The destabilizer is deficient in or absent from the S130 of cycloheximide-treated cells, indicating that it is labile or is repressed when translation is blocked. It is not a generic RNase, because it does not affect the turnover of .delta.-globin, .gamma.-globin, or histone mRNA and does not destabilize a major portion of polysomal polyadenylated mRNA. The destabilizer accelerates the turnover of the c-myc mRNA 3'' region, as well as subsequent 3''-to-5'' degradation of the mRNA body. It is inactivated in vitro by mild heating and by micrococcal nuclease, suggesting that it contains a nucleic acid component. c-myb mRNA is also destabilized in S130-supplemented in vitro reactions. Thes results imply that the stability of some mRNAs is regulated by cytosolic factors that are not associated with polysomes.