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.

The RNA-Binding Ubiquitin Ligase MEX3A Affects Glioblastoma Tumorigenesis by Inducing Ubiquitylation and Degradation of RIG-I

“…Here, we described for the first time that the RNA-binding MEX3A affects GB proliferation, acting as an E3-ubiquitin ligase. So far, little is known about the role of this protein in carcinogenesis [21][22][23][24]26]. Although MEX3A is a member of the RNA-binding ubiquitin ligase MEX3 protein family, its function as E3-ligase and its potential substrates have not yet been described.…”

“…Human MEX3 proteins consist of two N-terminal K homology (KH) domains, which provide RNA-binding ability, and a C-terminal RING finger module that confers ubiquitin E3-ligase activity [19]. MEX3 proteins play pivotal role in self-renewal and differentiation processes, with implications regarding stemness and carcinogenesis [20][21][22][23][24][25]. In particular, alterations of MEX3A activity have been described in gastric, colorectal and bladder cancers, although its mechanism of action and its potential substrates remain still elusive [21][22][23][24]26].…”

“…MEX3 proteins play pivotal role in self-renewal and differentiation processes, with implications regarding stemness and carcinogenesis [20][21][22][23][24][25]. In particular, alterations of MEX3A activity have been described in gastric, colorectal and bladder cancers, although its mechanism of action and its potential substrates remain still elusive [21][22][23][24]26]. To date, only the RING finger domain of human MEX3C has been functionally and structurally characterized, and Retinoic acid-inducible gene I (RIG-I) is the unique substrate described for this E3 ligase [27].…”

MEX3A knockdown inhibits the development of pancreatic ductal adenocarcinoma

“…The RNA-binding protein of evolutionarily conserved MEX3 family are first characterized in heterogeneous ribonucleoproteins, as mediators of post-transcriptional regulation in different organisms, participating in different physiological environments [12]. MEX3A has been identified to be associated with diseases, especially cancer, such as Wilms tumors [13], gastric carcinomas [14], colorectal carcinomas [15]. It is important to determine their effects on cancer development and assess their potential of cancer progression or prognosis.…”

RNA-Binding Protein Rnc1 Regulates Cell Length at Division and Acute Stress Response in Fission Yeast through Negative Feedback Modulation of the Stress-Activated Mitogen-Activated Protein Kinase Pathway

“…Rnc1 binds to mRNAs encoding SAPK components to promote their destabilization in vivo. RBPs recognize and bind target mRNA molecules in a sequencedependent as well as an independent manner and promote either their degradation or their stabilization (20). It has been shown elsewhere that a double mutation in the hallmark GxxG loop (GxxG to CDDG) impairs nucleic acid binding of KH domains without compromising their stability (2).…”