%0 Journal Article %J Neuron %D 2017 %T cTag-PAPERCLIP Reveals Alternative Polyadenylation Promotes Cell-Type Specific Protein Diversity and Shifts Araf Isoforms with Microglia Activation. %A Hwang, Hun-Way %A Saito, Yuhki %A Park, Christopher Y %A Blachère, Nathalie E %A Tajima, Yoko %A Fak, John J %A Zucker-Scharff, Ilana %A Darnell, Robert B %K Animals %K Antigens, Neoplasm %K Astrocytes %K Brain %K Cells, Cultured %K Female %K Humans %K Male %K Mice %K Microglia %K Nerve Tissue Proteins %K Neuro-Oncological Ventral Antigen %K Neurons %K Organ Specificity %K Polyadenylation %K Polypyrimidine Tract-Binding Protein %K Protein Isoforms %K Protein Serine-Threonine Kinases %K RNA-Binding Proteins %X

Alternative polyadenylation (APA) is increasingly recognized to regulate gene expression across different cell types, but obtaining APA maps from individual cell types typically requires prior purification, a stressful procedure that can itself alter cellular states. Here, we describe a new platform, cTag-PAPERCLIP, that generates APA profiles from single cell populations in intact tissues; cTag-PAPERCLIP requires no tissue dissociation and preserves transcripts in native states. Applying cTag-PAPERCLIP to profile four major cell types in the mouse brain revealed common APA preferences between excitatory and inhibitory neurons distinct from astrocytes and microglia, regulated in part by neuron-specific RNA-binding proteins NOVA2 and PTBP2. We further identified a role of APA in switching Araf protein isoforms during microglia activation, impacting production of downstream inflammatory cytokines. Our results demonstrate the broad applicability of cTag-PAPERCLIP and a previously undiscovered role of APA in contributing to protein diversity between different cell types and cellular states within the brain.

%B Neuron %V 95 %P 1334-1349.e5 %8 2017 Sep 13 %G eng %N 6 %1 https://www.ncbi.nlm.nih.gov/pubmed/28910620?dopt=Abstract %R 10.1016/j.neuron.2017.08.024