RNA Binding Proteins in Intestinal Epithelial Biology and Colorectal Cancer

Abstract

The intestinal epithelium is highly proliferative and consists of crypt invaginations that house stem cells and villus projections with differentiated cells. There exists a dynamic equilibrium between proliferation, migration, differentiation, and senescence that is regulated by several factors. Among these are RNA binding proteins (RBPs) that bind their targets in a both context dependent and independent manner. RBP-RNA complexes act as rheostats by regulating expression of RNAs both co- and post-transcriptionally. This is important, especially in response to intestinal injury, to fuel regeneration. The manner in which these RBPs function in the intestine and their interactions with other pivotal pathways in colorectal cancer may provide a framework for new insights and potential therapeutic applications.

Keywords: CUGBP Elav-Like Family Member 1 (CELF1); LIN28; MEX3A; Musashi (MSI); RNA binding protein 3 (RBM3) and Hu-Antigen R (HUR); RNA binding proteins; colorectal cancer; insulin-like growth factor 2 mRNA binding proteins (IGF2BP/IMP); intestinal stem cells.

Figure 1

Schematic representation of the crypt-villus axis and the major intestinal cell types for small intestine and colon The figure depicts the major cell types in the small intestine and colon. The stem cells reside at the crypt base and proliferate (transit amplifying cells) and differentiate into secretory (Paneth, enteroendocrine, goblet, tufts cells) and absorptive lineages (enterocytes). These differentiated cells migrate towards the villi (in the small intestine).

Figure 2

Schematic representation of the different functional roles of RBPs The figure depicts the major functional roles of the RBPs discussed in this review. The majority of the RBPs discussed here bind to mRNAs and regulate their processing (5′ capping, 3′ end processing, splicing), stability, localization and translation. This figure does not depict the non-conventional RBPs.

Figure 3

Schematic representation of the structural domains of the RBPs The figure shows a simplistic representation of the different structural domains of the RBPs discussed in this review that help them bind to their target RNAs and regulate their function. The amino acid length of the RBPs are also mentioned. The RBPs contain different types of RNA binding and catalytic domains including RRMs, KH domains, zinc finger domains and cold shock domains. Some of these RBPs also contain localization signals to help them shuttle in and out of the nucleas.