Mechanisms of mRNA localization in eukaryotic cells

描述(由申请人提供)： 在真核生物中，编码分泌性和整体膜蛋白的mRNAs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，在没有核糖体的情况下，mRNA与内质网结合。此外，最近的研究表明，编码胞浆蛋白的mRNAs可以翻译到内质网结合的多聚体上，在某些情况下，可以高度分割到内质网结合的多聚体上。因为这些mRNA不编码信号序列，所以SRP途径不太可能在它们运输到内质网的过程中发挥作用。因此，我们假设存在一条新的内质网导向的信使核糖核酸定位通路，该通路有助于控制细胞内信使核糖核酸分布的分割过程。在接下来的研究中，我们将确定mRNA与内质网结合的机制，并确定有助于内质网导向的mRNA定位的顺式和反式作用因子。我们建议的重点是内质网导向的mRNA定位的机制，有望识别在这一以前未被认识的和可能的基本mRNA分配途径中发挥作用的分子机制。

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.