Regulation and functional effects of localized RNAs

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

In the past year, we have provided a detailed molecular explanation of how targeting of specific mRNAs to protrusions contributes to efficient cell migration and invasion. Specifically, we have shown that the exact subcellular site of protein synthesis, as well as the kinetics of appearance of nascent chains, function as a 'partner-selection' mechanism that specify the binding partners and consequently the functional potential of newly-synthesized proteins. This study has been reported in BioRxiv and is currently in press in the journal Molecular Cell (Gasparski et al, Mol. Cell, in press). This study has provided an important conceptual advance through revealing a mechanism that can regulate the formation of protein complexes and the choice among multiple interacting partners. It has further provided an explanation and defined a new framework for understanding the need for precise mRNA compartmentalization and targeting even in small, dynamic cells. We have additionally described an experimental methodology for visualizing and quantifying mRNA localization at the invasive front of 3D cancer spheroids. This work was published as a chapter in a Methods in Molecular Biology book series on Cell Migration in Three Dimensions (Moissoglu et al., Methods Mol Biol, 2023). It presents a method to identify RNA spots in three-dimensional images and is tailored to quantitatively describe and compare distributions in the context of cells that exhibit front-back polarization. The analysis pipeline was implemented on mRNA distributions at the front cytoplasm of invasive leader cancer cells. However, it can be applicable in various other settings of front-back polarization or more broadly in cases of polarization along a linear axis. The analysis can additionally be applied in other cell types or methods of RNA imaging making it of broad potential applicability.