Massively parallel identification of mRNA localization elements in primary cortical neurons.

Nature neuroscience 2023 Mar

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Cells adopt highly polarized shapes and form distinct subcellular compartments in many cases due to the localization of many mRNAs to specific areas, where they are translated into proteins with local functions. This mRNA localization is mediated by specific cis-regulatory elements in mRNAs, commonly called 'zipcodes'. Although there are hundreds of localized mRNAs, only a few zipcodes have been characterized. Here we describe a novel neuronal zipcode identification protocol (N-zip) that can identify zipcodes across hundreds of 3' untranslated regions. This approach combines a method of separating the principal subcellular compartments of neurons-cell bodies and neurites-with a massively parallel reporter assay. N-zip identifies the let-7 binding site and (AU)n motif as de novo zipcodes in mouse primary cortical neurons. Our analysis also provides, to our knowledge, the first demonstration of an miRNA affecting mRNA localization and suggests a strategy for detecting many more zipcodes. © 2023. The Author(s).

Citation

Samantha Mendonsa, Nicolai von Kügelgen, Sayaka Dantsuji, Maya Ron, Laura Breimann, Artem Baranovskii, Inga Lödige, Marieluise Kirchner, Meret Fischer, Nadja Zerna, Lucija Bujanic, Philipp Mertins, Igor Ulitsky, Marina Chekulaeva. Massively parallel identification of mRNA localization elements in primary cortical neurons. Nature neuroscience. 2023 Mar;26(3):394-405