Preprint Highlight: mRNA Location and Translation Rate Determine Protein Targeting to Dual Destinations

NET1 is a guanine nucleotide exchange factor for RhoA GTPase that plays different roles in the nucleus and cytoplasm. While perinuclear and peripheral mRNA translation sites have been identified, the mechanisms of spatial translation regulation and impacts on protein function are not generally understood. Here, the authors use genetic tools to manipulate NET1 mRNA targeting sequences, as well as proximity ligation, mass spectrometry, and imaging. They show that mRNA localization, translation rate, and the order of appearance of targeting domains during translation determine the extent of protein synthesis in each location, promoting site-specific NET1 function. This novel regulation of protein targeting by RNA translation rate and location uncovers the potential to engineer mRNA localization to optimize protein function and will likely impact research on cell biology, immunology, and beyond. This preprint has been assigned the following badges: New Hypothesis, New Methods, Open Software, Cross-Validation. Read the preprint on bioRxiv ( Gasparski et al., 2023 ): https://doi.org/10.1101/2023.04.24.538105 .