Regulated Intron Removal Integrates Motivational State and Experience

Cell
Jason GillKausik Si

Abstract

Myriad experiences produce transient memory, yet, contingent on the internal state of the organism and the saliency of the experience, only some memories persist over time. How experience and internal state influence the duration of memory at the molecular level remains unknown. A self-assembled aggregated state of Drosophila Orb2A protein is required specifically for long-lasting memory. We report that in the adult fly brain the mRNA encoding Orb2A protein exists in an unspliced non-protein-coding form. The convergence of experience and internal drive transiently increases the spliced protein-coding Orb2A mRNA. A screen identified pasilla, the fly ortholog of mammalian Nova-1/2, as a mediator of Orb2A mRNA processing. A single-nucleotide substitution in the intronic region that reduces Pasilla binding and intron removal selectively impairs long-term memory. We posit that pasilla-mediated processing of unspliced Orb2A mRNA integrates experience and internal state to control Orb2A protein abundance and long-term memory formation.

Citations

Jul 22, 2018·Annual Review of Cell and Developmental Biology·Elisabetta Furlanis, Peter Scheiffele
Oct 13, 2018·PLoS Genetics·Raquel Barajas-AzpeletaKausik Si
Jun 27, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jenifer C Kaldun, Simon G Sprecher
Apr 25, 2020·Nucleic Acids Research·Zhi-Wei TanSuzanne Walker
Oct 24, 2020·The Journal of Biological Chemistry·Javier OrozDouglas V Laurents
Feb 21, 2021·Current Opinion in Cell Biology·Therese M Gerbich, Amy S Gladfelter
Jan 18, 2021·The Journal of Biological Chemistry·Javier OrozDouglas V Laurents
Mar 14, 2018·Trends in Cell Biology·Liying LiKausik Si
Apr 17, 2021·Frontiers in Behavioral Neuroscience·Camilla RoselliIsaac Cervantes-Sandoval
Jun 1, 2021·FEBS Open Bio·Marcos Gil-GarciaSalvador Ventura

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