Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, United States.
Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, United States.
Elife. 2018 Mar 26;7:e34042. doi: 10.7554/eLife.34042.
Alternative polyadenylation (APA) regulates mRNA translation, stability, and protein localization. However, it is unclear to what extent APA regulates these processes uniquely in specific cell types. Using a new technique, cTag-PAPERCLIP, we discovered significant differences in APA between the principal types of mouse cerebellar neurons, the Purkinje and granule cells, as well as between proliferating and differentiated granule cells. Transcripts that differed in APA in these comparisons were enriched in key neuronal functions and many differed in coding sequence in addition to 3'UTR length. We characterize , a transcript that shifted from expressing a short 3'UTR isoform to a longer one during granule cell differentiation. We show that regulates granule cell precursor proliferation and that its long 3'UTR isoform is targeted by miR-124, contributing to its downregulation during development. Our findings provide insight into roles for APA in specific cell types and establish a platform for further functional studies.
可变多聚腺苷酸化（APA）调节 mRNA 的翻译、稳定性和蛋白质定位。然而，APA 在多大程度上特异地调节特定细胞类型中的这些过程尚不清楚。我们使用一种新的技术 cTag-PAPERCLIP，发现了在主要类型的小鼠小脑神经元（浦肯野细胞和颗粒细胞）以及增殖和分化的颗粒细胞之间 APA 存在显著差异。在这些比较中 APA 不同的转录本在关键神经元功能中富集，并且许多转录本除了 3'UTR 长度之外，在编码序列上也存在差异。我们描述了一个在颗粒细胞分化过程中从表达短 3'UTR 亚型转变为长 3'UTR 亚型的转录本。我们表明，调控颗粒细胞前体细胞的增殖，并且其长 3'UTR 亚型被 miR-124 靶向，有助于其在发育过程中的下调。我们的发现为 APA 在特定细胞类型中的作用提供了深入的了解，并为进一步的功能研究建立了一个平台。
