The Rab5 effector FERRY links early endosomes with mRNA localization.

Molecular cell 2023 Jun 01

filter terms:

Localized translation is vital to polarized cells and requires precise and robust distribution of different mRNAs and ribosomes across the cell. However, the underlying molecular mechanisms are poorly understood and important players are lacking. Here, we discovered a Rab5 effector, the five-subunit endosomal Rab5 and RNA/ribosome intermediary (FERRY) complex, that recruits mRNAs and ribosomes to early endosomes through direct mRNA-interaction. FERRY displays preferential binding to certain groups of transcripts, including mRNAs encoding mitochondrial proteins. Deletion of FERRY subunits reduces the endosomal localization of transcripts in cells and has a significant impact on mRNA levels. Clinical studies show that genetic disruption of FERRY causes severe brain damage. We found that, in neurons, FERRY co-localizes with mRNA on early endosomes, and mRNA loaded FERRY-positive endosomes are in close proximity of mitochondria. FERRY thus transforms endosomes into mRNA carriers and plays a key role in regulating mRNA distribution and transport. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Jan S Schuhmacher, Susanne Tom Dieck, Savvas Christoforidis, Cedric Landerer, Jimena Davila Gallesio, Lena Hersemann, Sarah Seifert, Ramona Schäfer, Angelika Giner, Agnes Toth-Petroczy, Yannis Kalaidzidis, Katherine E Bohnsack, Markus T Bohnsack, Erin M Schuman, Marino Zerial. The Rab5 effector FERRY links early endosomes with mRNA localization. Molecular cell. 2023 Jun 01;83(11):1839-1855.e13