Conway G, Wooley J, Bibring T, LeStourgeon W M
Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee 37235.
Mol Cell Biol. 1988 Jul;8(7):2884-95. doi: 10.1128/mcb.8.7.2884-2895.1988.
An assay for the in vitro assembly of HeLa cell 40S nuclear ribonucleoprotein particles (hnRNP particles) has been developed. The substrates were single-stranded nucleic acid polymers of defined length and sequence prepared in vitro and the six major core particle proteins from isolated 40S hnRNP. The fidelity of in vitro assembly was evaluated on various physical parameters, including sedimentation, salt dissociation, polypeptide stoichiometry, UV-activated protein-RNA cross-linking, and overall morphology. Correct particle assembly depended on RNA length and on the input protein/RNA ratio but not on the concentration of the reactant mixture nor on the presence or absence of internal RNA processing signals, a 5'-cap structure, a 3'-poly(A) moiety, or ATP as energy source. RNA lengths between 685 and 726 nucleotides supported correct particle assembly. Dimers and oligomeric complexes that possessed the same polypeptide stoichiometry as native hnRNP assembled on RNA chains that were integral multiples of 700 nucleotides. Intermediate-length RNA supported the assembly of nonstoichiometric complexes lacking structural homogeneity. An analysis of these complexes indicates that proteins A1 and A2 may be the first proteins to bind RNA during particle assembly. We conclude that the major proteins of 40S hnRNP particles contain the necessary information for packaging nascent transcripts into a repeating "ribonucleosomal" structure possessing a defined RNA length and protein composition but do not themselves contain the information for modulating packaging that may be required for RNA splicing.
已开发出一种用于体外组装HeLa细胞40S核糖核蛋白颗粒(hnRNP颗粒)的检测方法。底物是体外制备的具有确定长度和序列的单链核酸聚合物,以及从分离的40S hnRNP中提取的六种主要核心颗粒蛋白。通过各种物理参数评估体外组装的保真度,包括沉降、盐解离、多肽化学计量、紫外线激活的蛋白质-RNA交联以及整体形态。正确的颗粒组装取决于RNA长度和输入的蛋白质/RNA比例,而不取决于反应物混合物的浓度,也不取决于内部RNA加工信号、5'-帽结构、3'-聚(A)部分或作为能量来源的ATP的存在与否。685至726个核苷酸之间的RNA长度支持正确的颗粒组装。在700个核苷酸的整数倍的RNA链上组装的二聚体和寡聚复合物,其多肽化学计量与天然hnRNP相同。中等长度的RNA支持缺乏结构同质性的非化学计量复合物的组装。对这些复合物的分析表明,蛋白质A1和A2可能是颗粒组装过程中首先与RNA结合的蛋白质。我们得出结论,40S hnRNP颗粒的主要蛋白质包含将新生转录本包装成具有确定RNA长度和蛋白质组成的重复“核糖核小体”结构所需的必要信息,但它们本身并不包含RNA剪接可能需要的调节包装的信息。