Hierarchical regulation of mRNA partitioning between the cytoplasm and the endoplasmic reticulum of mammalian cells.
Hierarchical regulation of mRNA partitioning between the cytoplasm and the endoplasmic reticulum of mammalian cells.
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DOI：
10.1091/mbc.e11-03-0239
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发表时间：
2011-07-15
影响因子：
3.3
通讯作者：
Nicchitta CV
中科院分区：
文献类型：
--
作者：
Chen Q;Jagannathan S;Reid DW;Zheng T;Nicchitta CV
这项研究揭示了mRNAs在胞浆和内质网(ER)之间的分层划分方式，并确定了ER在全球蛋白质合成中的重要作用。定义了两种核糖体依赖和非核糖体依赖的mRNA与内质网结合方式。目前认为，mRNA转录组通过二元选择被分配在胞浆和内质网(ER)之间；编码胞浆/核质蛋白的mRNAs翻译在游离的核糖体上，编码拓扑性信号承载蛋白的mRNAs翻译在ER结合的核糖体上，ER的定位由信号识别粒子途径决定。在亚细胞mRNA划分的亚基因组和基因组分析中，我们报告了胞浆/核质和拓扑信号编码的mRNAs的重叠亚细胞分布，这两个队列的mRNAs都显示出非规范的亚细胞划分模式。出乎意料的是，拓扑信号编码的mRNA转录组被观察到以一种分层的、队列特有的方式进行划分。编码内膜系统驻留蛋白的mRNAs聚集在高ER富集值，而编码分泌途径货物的mRNAs广泛表达在游离和内质网结合的核糖体上。有两种截然不同的信使核糖核酸与内质网关联的模式被识别。编码内膜驻留蛋白的mRNAs通过直接的、非依赖于核糖体的相互作用结合，而编码分泌性货物的mRNAs主要表现为核糖体依赖的内质网结合模式。这些数据表明，mRNAs通过固有的和编码的拓扑发生信号的分级系统在细胞质和内质网之间被分割，并识别与内质网相关的mRNA队列受限模式。
This study reveals that mRNAs are partitioned between the cytosol and endoplasmic reticulum (ER) compartments in a hierarchical manner and identifies a prominent role for the ER in global protein synthesis. Two modes of mRNA association with the ER are defined: ribosome dependent and ribosome independent. The mRNA transcriptome is currently thought to be partitioned between the cytosol and endoplasmic reticulum (ER) compartments by binary selection; mRNAs encoding cytosolic/nucleoplasmic proteins are translated on free ribosomes, and mRNAs encoding topogenic signal-bearing proteins are translated on ER-bound ribosomes, with ER localization being conferred by the signal-recognition particle pathway. In subgenomic and genomic analyses of subcellular mRNA partitioning, we report an overlapping subcellular distribution of cytosolic/nucleoplasmic and topogenic signal-encoding mRNAs, with mRNAs of both cohorts displaying noncanonical subcellular partitioning patterns. Unexpectedly, the topogenic signal-encoding mRNA transcriptome was observed to partition in a hierarchical, cohort-specific manner. mRNAs encoding resident proteins of the endomembrane system were clustered at high ER-enrichment values, whereas mRNAs encoding secretory pathway cargo were broadly represented on free and ER-bound ribosomes. Two distinct modes of mRNA association with the ER were identified. mRNAs encoding endomembrane-resident proteins were bound via direct, ribosome-independent interactions, whereas mRNAs encoding secretory cargo displayed predominantly ribosome-dependent modes of ER association. These data indicate that mRNAs are partitioned between the cytosol and ER compartments via a hierarchical system of intrinsic and encoded topogenic signals and identify mRNA cohort-restricted modes of mRNA association with the ER.