Pouya Sarvari, Karla Rubio, Stephanie Dobersch, Aglaia Ntokou, and Verónica Vallejo-Ruiz
Therapeutic targeting of splicin gvariants in cancer
Abstract
The cellular process of removing introns from pre-mRNAs and connecting the remaining exons to produce a mature mRNA is termed mRNA splicing. However, exons from the same pre-mRNA can be joined indifferent combinations by AlternativeSplicing(AS), generating diversified mRNA transcripts which can be translated to produce proteins with distinct functions and structures, and yetarise from asingle gene. Thus, AS is an essential lregulator of gene expression and proteome diversity. Nearly all multi-exongenes undergo AS executed by the spliceosome, regulated by various RNA-bindin gproteins (RBPs), and aided by cis-actingelements and trans-acting factors. Aberrations in AS lead to tumorigenesis due to either mutation in splicing-regulatory elements of specific cancer genes, a mutation with in canonical RNA splicing sites influencing mRNA maturation, or even alterations in the regulatory splicing machinery. Understanding AS in cancer cells would give us better in sights into tumor biology and better therapeutic means to control tumor progression.
