Gill Jason, Park Younshim, McGinnis J P, Perez-Sanchez Consuelo, Blanchette Marco, Si Kausik
Stowers Institute for Medical Research, 1000E 50(th) Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA.
Stowers Institute for Medical Research, 1000E 50(th) Street, Kansas City, MO 64110, USA.
Cell. 2017 May 18;169(5):836-848.e15. doi: 10.1016/j.cell.2017.05.006.
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.
无数的经历产生短暂的记忆，然而，取决于生物体的内部状态和经历的显著性，只有一些记忆会随着时间的推移而持续存在。在分子水平上，经历和内部状态如何影响记忆的持续时间仍然未知。果蝇Orb2A蛋白的一种自组装聚集状态是持久记忆所特需的。我们报道，在成年果蝇大脑中，编码Orb2A蛋白的mRNA以未剪接的非蛋白质编码形式存在。经历和内部驱动的共同作用会短暂增加剪接后的蛋白质编码Orb2A mRNA。一项筛选鉴定出果蝇中与哺乳动物Nova-1/2直系同源的pasilla，作为Orb2A mRNA加工的介导因子。内含子区域的单核苷酸取代会减少Pasilla的结合并选择性地损害内含子去除，从而损害长期记忆。我们认为，pasilla介导的未剪接Orb2A mRNA的加工整合了经历和内部状态，以控制Orb2A蛋白丰度和长期记忆形成。
