Regulation and functional effects of localized RNAs

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Over the past year, our research has made substantial advances in understanding the spatial regulation of mRNA localization and its role in cell and tissue dynamics-processes that are increasingly recognized as critical to cancer progression and metastasis. Our work has culminated in two high-impact publications that define novel molecular mechanisms linking mRNA trafficking to cell behavior and tissue architecture. In Cell Reports (Moissoglu et al., 2025), we identified a previously uncharacterized motor-adaptor complex involving the kinesin motor protein KIF1C and the RNA-binding protein CNBP. This KIF1C-CNBP complex plays a central role in trafficking specific mRNAs to the leading edges of migrating cells. By facilitating the localized translation of these mRNAs, the complex supports dynamic changes in cell shape and motility. These findings shed light on how cancer cells spatially coordinate gene expression to enable invasive behaviors, suggesting new points of intervention to disrupt metastatic dissemination. Complementing this work, our study in Nature Communications (Mason et al., 2025) investigated how mRNA localization contributes to epithelial tissue organization. We demonstrated that proper spatial distribution of specific mRNAs is necessary for maintaining connections of epithelial tissues with the underlying stroma. Disruption of this RNA localization machinery leads to disorganized tissue architecture-a hallmark of early tumorigenesis. This work provides mechanistic insights into how loss of RNA localization fidelity could initiate or accelerate epithelial-to-mesenchymal transitions during cancer progression. Together, these studies advance our understanding of the spatial regulation of gene expression at the RNA level and highlight its significance in both individual cancer cell behavior and multicellular tissue integrity. These insights open new avenues for developing therapies that target RNA transport mechanisms to limit cancer spread and preserve tissue homeostasis.