title: Genomic analyses of the RNA-binding protein Hu antigen R (HuR) identify a complex network of target genes and novel characteristics of its binding sites.
abstract: The ubiquitously expressed RNA-binding protein Hu antigen R (HuR) or ELAVL1 is implicated in a variety of biological processes as well as being linked with a number of diseases, including cancer. Despite a great deal of prior investigation into HuR, there is still much to learn about its function. We take an important step in this direction by conducting cross-linking and immunoprecipitation and RNA sequencing experiments followed by an extensive computational analysis to determine the characteristics of the HuR binding site and impact on the transcriptome. We reveal that HuR targets predominantly uracil-rich single-stranded stretches of varying size, with a strong conservation of structure and sequence composition. Despite the fact that HuR sites are observed in intronic regions, our data do not support a role for HuR in regulating splicing. HuR sites in 3'-UTRs overlap extensively with predicted microRNA target sites, suggesting interplay between the functions of HuR and microRNAs. Network analysis showed that identified targets containing HuR binding sites in the 3' UTR are highly interconnected.
authors: Molecular and Computational Biology, University of Southern California, Los Angeles, California 90089, USA.
authors: Philip J
authors: PJ
authors: Uren
authors: Suzanne C
authors: SC
authors: Burns
authors: Jianhua
authors: J
authors: Ruan
authors: Kusum K
authors: KK
authors: Singh
authors: Andrew D
authors: AD
authors: Smith
authors: Luiz O F
authors: LO
authors: Penalva
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology*; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D023281:Genomics / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; D051959:ELAV Proteins; D035683:MicroRNAs