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@ARTICLE{Sommerkamp:154285,
author = {P. Sommerkamp$^*$ and S. Altamura and S. Renders$^*$ and A.
Narr$^*$ and L. Ladel$^*$ and P. Zeisberger$^*$ and P. L.
Eiben$^*$ and M. Fawaz and M. A. Rieger$^*$ and N.
Cabezas-Wallscheid$^*$ and A. Trumpp$^*$},
title = {{D}ifferential {A}lternative {P}olyadenylation {L}andscapes
{M}ediate {H}ematopoietic {S}tem {C}ell {A}ctivation and
{R}egulate {G}lutamine {M}etabolism.},
journal = {Cell stem cell},
volume = {26},
number = {5},
issn = {1934-5909},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2020-00711},
pages = {722-738.e7},
year = {2020},
note = {DKFZ-ZMBH Alliance2020 May
7;26(5):722-738.e7#EA:A010#LA:A010#},
abstract = {Alternative polyadenylation (APA) is emerging as an
important regulatory mechanism of RNA and protein isoform
expression by controlling 3' untranslated region (3'-UTR)
composition. The relevance of APA in stem cell hierarchies
remains elusive. Here, we first demonstrate the requirement
of the APA regulator Pabpn1 for hematopoietic stem cell
(HSC) function. We then determine the genome-wide APA
landscape (APAome) of HSCs and progenitors by performing
low-input 3' sequencing paired with bioinformatic pipelines.
This reveals transcriptome-wide dynamic APA patterns and an
overall shortening of 3'-UTRs during differentiation and
upon homeostatic or stress-induced transition from
quiescence to proliferation. Specifically, we show that APA
regulates activation-induced Glutaminase (Gls) isoform
switching by Nudt21. This adaptation of the glutamine
metabolism by increasing the GAC:KGA isoform ratio fuels
versatile metabolic pathways necessary for HSC self-renewal
and proper stress response. Our study establishes APA as a
critical regulatory layer orchestrating HSC self-renewal,
behavior, and commitment.},
cin = {A010 / HD01 / V960},
ddc = {570},
cid = {I:(DE-He78)A010-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)V960-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32229311},
doi = {10.1016/j.stem.2020.03.003},
url = {https://inrepo02.dkfz.de/record/154285},
}