TY - JOUR
T1 - Biology of the mrna splicing machinery and its dysregulation in cancer providing therapeutic opportunities
AU - Blijlevens, Maxime
AU - Li, Jing
AU - van Beusechem, Victor W.
N1 - Funding Information: Funding: This research was supported by the Walter Bruckerhoff Stiftung and the China Scholar‐ ship Counsil (no. 201807040045). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5/2
Y1 - 2021/5/2
N2 - Dysregulation of messenger RNA (mRNA) processing—in particular mRNA splicing—is a hallmark of cancer. Compared to normal cells, cancer cells frequently present aberrant mRNA splicing, which promotes cancer progression and treatment resistance. This hallmark provides op-portunities for developing new targeted cancer treatments. Splicing of precursor mRNA into mature mRNA is executed by a dynamic complex of proteins and small RNAs called the spliceosome. Spliceosomes are part of the supraspliceosome, a macromolecular structure where all co‐transcrip-tional mRNA processing activities in the cell nucleus are coordinated. Here we review the biology of the mRNA splicing machinery in the context of other mRNA processing activities in the su-praspliceosome and present current knowledge of its dysregulation in lung cancer. In addition, we review investigations to discover therapeutic targets in the spliceosome and give an overview of inhibitors and modulators of the mRNA splicing process identified so far. Together, this provides insight into the value of targeting the spliceosome as a possible new treatment for lung cancer.
AB - Dysregulation of messenger RNA (mRNA) processing—in particular mRNA splicing—is a hallmark of cancer. Compared to normal cells, cancer cells frequently present aberrant mRNA splicing, which promotes cancer progression and treatment resistance. This hallmark provides op-portunities for developing new targeted cancer treatments. Splicing of precursor mRNA into mature mRNA is executed by a dynamic complex of proteins and small RNAs called the spliceosome. Spliceosomes are part of the supraspliceosome, a macromolecular structure where all co‐transcrip-tional mRNA processing activities in the cell nucleus are coordinated. Here we review the biology of the mRNA splicing machinery in the context of other mRNA processing activities in the su-praspliceosome and present current knowledge of its dysregulation in lung cancer. In addition, we review investigations to discover therapeutic targets in the spliceosome and give an overview of inhibitors and modulators of the mRNA splicing process identified so far. Together, this provides insight into the value of targeting the spliceosome as a possible new treatment for lung cancer.
KW - Alternative splicing
KW - NSCLC
KW - Splicing dysregulation
KW - Splicing factors
UR - http://www.scopus.com/inward/record.url?scp=85105487384&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms22105110
DO - https://doi.org/10.3390/ijms22105110
M3 - Review article
C2 - 34065983
SN - 1661-6596
VL - 22
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 10
M1 - 5110
ER -