Myra Halpin

      Gene expression is the process by which cells interpret the code of DNA by producing a messenger RNA (mRNA) copy, which serves as a template for a protein. Gene expression control is a vital process in the normal function of cells, controlling the timing of virtually all cellular events, and occurs at each level of expression from DNA to protein. RNA-binding proteins (RBPs) interact with target messenger mRNA molecules to control gene expression at the RNA level. An emergent property of this is a complex network of RBPs, in which a certain mRNA can have several RBPs bound at once in a time- and sequence-dependent manner, resulting in tight control of processing.

HuR is an RBP which is highly expressed in all human tissues. Increased levels of HuR are associated with several cancers, such as colon and brain. HuR is known to bind mRNA molecules and increase their stability. Owing to the ubiquity and high expression of HuR, full characterization of HuR is critical to a complete picture of RNA-level gene regulation in cells.

      Recent studies have used a novel technique to determine the binding sites of HuR across the set of cellular RNA. Surprisingly, the study found binding sites in sequences called introns which are removed in producing mature mRNA in a process called splicing. This suggests that HuR not only targets mature mRNA, but also targets immature pre-mRNA.

      We analyzed RNA bound to HuR to show that HuR can bind intronic sequences in immature mRNA. We also depleted HuR in human cells and showed HuR-intron binding causes a functional effect on pre-mRNA stability, such that decreasing HuR levels decreases the target pre-mRNA levels. Our results suggest that HuR plays a role in either pre-mRNA splicing or splicing-concurrent processing steps, which gives insight into the previously less-considered nuclear function of HuR, and adds another role for HuR in RNA regulation.