Biology of the mrna splicing machinery and its dysregulation in cancer providing therapeutic opportunities

Maxime Blijlevens, Jing Li, Victor W. van Beusechem*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number5110
JournalInternational Journal of Molecular Sciences
Volume22
Issue number10
DOIs
Publication statusPublished - 2 May 2021

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