Mechanisms of mRNA localization in eukaryotic cells

描述（由申请人提供）： 在真核生物中，编码分泌和整合膜蛋白的mRNA通过信号识别颗粒（SRP）途径选择性地分配到内质网（ER）。然而，早期的研究表明，mRNA结合的ER在核糖体的情况下。此外，最近的研究表明，编码胞浆蛋白的mRNA可以在ER结合的多核糖体上翻译，并且在某些情况下，高度分配到ER结合的多核糖体。因为这些mRNA不编码信号序列，所以SRP途径不太可能在它们向ER的运输中起作用。因此，我们假设，一种新的，ER-指导的mRNA定位途径存在，有助于管理mRNA在细胞中的分布的分配过程。在下面的研究中，我们将确定与ER mRNA协会的机制，并确定顺式和反式作用的因素，有助于ER定向mRNA定位。我们提出的重点是ER-指导mRNA定位的机制，预计将产生识别的分子机制，在这个以前不受重视的和可能的基本mRNA分配途径。

DESCRIPTION (provided by applicant): In eukaryotes, mRNAs encoding secretory and integral membrane proteins are selectively partitioned to the endoplasmic reticulum (ER) via the signal recognition particle (SRP) pathway. However, early studies suggest that mRNA binds to the ER in the absence of ribosomes. Furthermore, recent studies demonstrate that mRNAs encoding cytosolic proteins can be translated on and, in some cases, highly partitioned to ER bound polysomes. Because these mRNAs do not encode for signal sequences, it is unlikely that the SRP pathway functions in their trafficking to the ER. Thus, we hypothesize that a novel, ER-directed mRNA localization pathway exists that contributes to the partitioning processes governing mRNA distribution in the cell. In the following studies we will define the mechanism of mRNA association with the ER and identify cis and trans acting factors that contribute to ER-directed mRNA localization. Our proposed focus on the mechanism of ER-directed mRNA localization is expected to yield the identification of the molecular machinery functioning in this previously unappreciated and likely fundamental mRNA partitioning pathway.