MicroRNAs, Tristetraprolin Family Members and HuR: A Complex Interplay Controlling Cancer-Related Processes

Abstract

MicroRNAs represent the most characterized post-transcriptional regulators of gene expression. Their altered expression importantly contributes to the development of a wide range of metabolic and inflammatory diseases but also cancers. Accordingly, a myriad of studies has suggested novel therapeutic approaches aiming at inhibiting or restoring the expression of miRNAs in human diseases. However, the influence of other trans-acting factors, such as long-noncoding RNAs or RNA-Binding-Proteins, which compete, interfere, or cooperate with miRNAs-dependent functions, indicate that this regulatory mechanism is much more complex than initially thought, thus questioning the current models considering individuals regulators. In this review, we discuss the interplay existing between miRNAs and the AU-Rich Element Binding Proteins (AUBPs), HuR and tristetraprolin family members (TTP, BRF1 and BRF2), which importantly control the fate of mRNA and whose alterations have also been associated with the development of a wide range of chronic disorders and cancers. Deciphering the interplay between these proteins and miRNAs represents an important challenge to fully characterize the post-transcriptional regulation of pro-tumorigenic processes and design new and efficient therapeutic approaches.

Synergistic roles of tristetraprolin family members in myeloid cells in the control of inflammation

“…This phenomenon has been observed in experiments of this type in many different cell types, and there is no simple explanation ( Patial et al, 2016b ). One possibility is that the potential binding sites could be occupied by other AU-rich element-binding proteins or even other RNAs ( Sobolewski et al, 2022 ). Another possibility is that there could be an RNA secondary structure involving the potential binding site, which has been shown to prevent binding by TTP family proteins ( Hudson et al, 2004 ).…”

MiRNAs in Alcohol-Related Liver Diseases and Hepatocellular Carcinoma: A Step toward New Therapeutic Approaches?

“…The pre-miRNA is exported from the nucleus to the cytosol by the Exportin5/RanGTP. In the cytosol, the pre-miRNA is processed by the RNase III endonuclease Dicer, which removes the terminal loop of the pri-miRNA thereby producing a mature miRNA duplex, composed of a guide strand and a complementary passenger strand [34]. According to the canonical model, the passenger strand is degraded, while the guide strand is maintained and is incorporated into the RNA-Induced Silencing Complex (RISC) to settle at the complementary sequences in the 3 UTRs of their target's mRNAs.…”

“…Conversely, one mRNA can be regulated by several miRNAs [30,35]. Moreover, our understanding of miRNAs-dependent regulation is challenged by the interplay between miRNAs, long non-coding RNA (lncRNAs), and RNA Binding Proteins (RBPs), which importantly control the expression, but also the bioavailability and activity of miRNAs [34]. While most studies are focusing on miRNAs with a deregulated expression pattern, increasing evidence indicates that the expression does not always correlate with the activity of miRNAs.…”

Long Non-Coding RNA Generated fromCDKN1AGene by Alternative Polyadenylation Regulates p21 Expression during DNA Damage Response

“…HuR can bind not only the 3' untranslated region (3'UTR) of full-length mRNAs, regulating their stability (35,58), but also lncRNAs, affecting their stability and localization (59)(60). In fact, intronic HuR sites are more prevalent than 3'UTR binding regions (61).…”