cTag-PAPERCLIP Reveals Alternative Polyadenylation Promotes Cell-Type Specific Protein Diversity and Shifts Araf Isoforms with Microglia Activation.

Abstract:

: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.

journal_name

Neuron

journal_title

Neuron

authors

Hwang HW,Saito Y,Park CY,Blachère NE,Tajima Y,Fak JJ,Zucker-Scharff I,Darnell RB

doi

10.1016/j.neuron.2017.08.024

subject

Has Abstract

pub_date

2017-09-13 00:00:00

pages

1334-1349.e5

issue

6

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(17)30739-0

journal_volume

95

pub_type

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