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@ARTICLE{Duggimpudi:858402,
author = {Duggimpudi, Sujitha and Kloetgen, Andreas and Maney,
Sathish Kumar and Münch, Philipp C. and Hezaveh, Kebria and
Shaykhalishahi, Hamed and Hoyer, Wolfgang and McHardy, Alice
C. and Lang, Philipp A. and Borkhardt, Arndt and Hoell,
Jessica I.},
title = {{T}ranscriptome-wide analysis uncovers the targets of the
{RNA}-binding protein {MSI}2 and effects of {MSI}2's
{RNA}-binding activity on {IL}-6 signaling},
journal = {The journal of biological chemistry},
volume = {293},
number = {40},
issn = {1083-351X},
address = {Bethesda, Md.},
publisher = {Soc.72889},
reportid = {FZJ-2018-07288},
pages = {15359 - 15369},
year = {2018},
abstract = {The RNA-binding protein Musashi 2 (MSI2) has emerged as an
important regulator in cancer initiation, progression, and
drug resistance. Translocations and deregulation of the MSI2
gene are diagnostic of certain cancers, including chronic
myeloid leukemia (CML) with translocation t(7;17), acute
myeloid leukemia (AML) with translocation t(10;17), and some
cases of B-precursor acute lymphoblastic leukemia (pB-ALL).
To better understand the function of MSI2 in leukemia, the
mRNA targets that are bound and regulated by MSI2 and their
MSI2-binding motifs need to be identified. To this end,
using photoactivatable ribonucleoside cross-linking and
immunoprecipitation (PAR-CLIP) and the Multiple EM for Motif
Elicitation (MEME) analysis tool, here we identified
MSI2’s mRNA targets and the consensus RNA-recognition
element (RRE) motif recognized by MSI2 (UUAG). Of note, MSI2
knockdown altered the expression of several genes with roles
in eukaryotic initiation factor 2 (eIF2), hepatocyte growth
factor (HGF), and epidermal growth factor (EGF) signaling
pathways. We also show that MSI2 regulates classic
interleukin-6 (IL-6) signaling by promoting the degradation
of the mRNA of IL-6 signal transducer (IL6ST or GP130),
which, in turn, affected the phosphorylation statuses of
signal transducer and activator of transcription 3 (STAT3)
and the mitogen-activated protein kinase ERK. In summary, we
have identified multiple MSI2-regulated mRNAs and provided
evidence that MSI2 controls IL6ST activity that control
oncogenic signaling networks. Our findings may help inform
strategies for unraveling the role of MSI2 in leukemia to
pave the way for the development of targeted therapies.},
cin = {ICS-6},
ddc = {540},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30126842},
UT = {WOS:000446549200003},
doi = {10.1074/jbc.RA118.002243},
url = {https://juser.fz-juelich.de/record/858402},
}