Adaptive and maladaptive expression of the mRNA regulatory protein HuR

Abstract

The RNA-binding proteins involved in regulation of mRNA post-transcriptional processing and translation control the fates of thousands of mRNA transcripts and basic cellular processes. The best studied of these, HuR, is well characterized as a mediator of mRNA stability and translation, and more recently, as a factor in nuclear functions such as pre-mRNA splicing. Due to HuR’s role in regulating thousands of mRNA transcripts, including those for other RNA-binding proteins, HuR can act as a master regulator of cell survival and proliferation. HuR itself is subject to multiple post-translational modifications including regulation of its nucleocytoplasmic distribution. However, the mechanisms that govern HuR levels in the cell have only recently begun to be defined. These mechanisms are critical to cell health, as it has become clear in recent years that aberrant expression of HuR can lead alternately to decreased cell viability or to promotion of pathological proliferation and invasiveness. HuR is expressed as alternate mRNAs that vary in their untranslated regions, leading to differences in transcript stability and translatability. Multiple transcription factors and modulators of mRNA stability that regulate HuR mRNA expression have been identified. In addition, translation of HuR is regulated by numerous microRNAs, several of which have been demonstrated to have anti-tumor properties due to their suppression of HuR expression. This review summarizes the current state of knowledge of the factors that regulate HuR expression, along with the circumstances under which these factors contribute to cancer and inflammation.

Keywords: HuR; RNA binding proteins; Transcription; RNA stability; Translation; Protein stability; Cell stress; MicroRNAs; Cancer

Core tip: HuR is an RNA-binding protein that regulates post-transcriptional processing of thousands of mRNAs, including many that encode proteins that are critical to basic cellular functions. Thus, while loss of HuR can lead to cell death, pathological overexpression of HuR is associated with numerous types of cancer. However, the mechanisms that govern expression of HuR have only begun to be delineated. This review summarizes the current state of knowledge of these mechanisms and how they may contribute to cell survival and pathology.