Interaction between mRNA, ribosomes and the cytoskeleton.
Interaction between mRNA, ribosomes and the cytoskeleton.
复制标题
mRNA、核糖体和细胞骨架之间的相互作用。
作者：
J. Hesketh;I. Pryme
所有细胞的一个主要后勤问题是新合成的蛋白质如何被引导到它们适当的亚细胞位置。目前，人们对大多数蛋白质如何靶向其功能位点知之甚少。在膜和分泌蛋白的情况下，已知这种靶向的第一步是通过在不同的多核糖体（多核糖体）隔室中合成来实现的。有充分的证据表明，膜蛋白和分泌蛋白是在与粗面内质网（ER）膜结合的多聚核糖体（膜结合多聚核糖体; MBP）上合成的，并且有人提出其他细胞蛋白是在所谓的“自由”细胞溶质多聚核糖体（FP）上合成的（参见Shires & Pitot的评论，1973年; Svardal & Pryme，1980年）。因此，根据编码蛋白的最终细胞定位，mRNA被设想为被分离成两个不同的多聚核糖体群体（信号假说;参见Blobel和Dobberstein，1975）。已经计算出，在肝细胞中从细胞核释放的总共15000种（Adesnik和Maschio，1981）中，约500-2000种mRNA种类含有信号序列，并且如此选择用于在MBP上翻译。直到最近，人们一直认为编码大部分细胞蛋白质的剩余mRNA在FP上翻译。然而，在过去的10年中，这两种多聚核糖体群体之间蛋白质合成的简单划分受到质疑，因为积累的证据表明，一些mRNA和多聚核糖体与细胞骨架（细胞骨架结合的多聚核糖体; CBP）相关。细胞骨架由微丝、中间丝和微管的胞质网络以及假定的微梁晶格组成。翻译装置和细胞骨架的细丝系统之间的相互作用的含义对于蛋白质合成的组织具有相当重要的意义。因此，如果FP、CBP和MBP合成不同的蛋白质，那么多聚核糖体与细胞骨架的结合可能是细胞能够对其新合成的蛋白质进行分类的关键特征。另外，mRNA与细胞骨架的结合可能在mRNA从细胞核向细胞质的转运中起重要作用（Agutter，1988，1990）。本综述的目的是评估翻译装置组分与细胞骨架相关的证据（Nielsen等人，1983年），然后讨论什么是已知的生物化学性质和生理意义的这种相互作用。
A major logistical problem for all cells is how newly synthesized proteins are directed to their appropriate subcellular location. Currently, little is known of how the majority of proteins are targeted to their site of function. In the case of membrane and secretory proteins it is known that the first step in such targeting is achieved by synthesis in a distinct polyribosome (polysome) compartment. It is well documented that membrane and secreted proteins are synthesized on polysomes bound to rough endoplasmic reticulum (ER) membranes (membrane-bound polysomes; MBP) and it has been proposed that the other cell proteins are made on the so-called 'free' cytosolic polysomes (FP) (see reviews by Shires & Pitot, 1973; Svardal & Pryme, 1980). Thus, mRNAs were envisaged as being segregated into two distinct populations of polysomes depending on the ultimate cellular localization of the encoded protein (the signal hypothesis; see Blobel & Dobberstein, 1975). It has been calculated that some 500-2000 mRNA species, out of a total of 15000 (Adesnik & Maschio, 1981) that are released from the nucleus in liver cells, contain a signal sequence and are so selected for translation on MBP. It has been assumed until recently that the remaining mRNAs, which code for the bulk of cell proteins, are translated on FP. A simple division of protein synthesis between these two polysome populations has been questioned during the past 10 years, however, since evidence has accumulated which suggests that some mRNAs and polysomes are associated with the cytoskeleton (cytoskeletal-bound polysomes; CBP). The cytoskeleton consists of cytoplasmic networks of microfilaments, intermediate filaments and microtubules together with the postulated microtrabecular lattice. The implications of interactions between the translational apparatus and the filament systems of the cytoskeleton are of considerable significance concerning the organization of protein synthesis. Thus if FP, CBP and MBP synthesize different proteins, then an association of a population of polysomes with the cytoskeleton could be a key feature in the way the cell is able to sort its newly synthesized proteins. Alternatively the association of mRNAs with the cytoskeleton might be important in the transport ofmRNA from nucleus to cytoplasm (Agutter, 1988, 1990). The aims of the present review are to evaluate the evidence for the association of components of the translational apparatus with the cytoskeleton (reviewed earlier by Nielsen et al., 1983) and then to discuss what is known about the biochemical nature and physiological significance of such interactions.