title: Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.
abstract: RNA-binding proteins coordinate the fates of multiple RNAs, but the principles underlying these global interactions remain poorly understood. We elucidated regulatory mechanisms of the RNA-binding protein HuR, by integrating data from diverse high-throughput targeting technologies, specifically PAR-CLIP, RIP-chip, and whole-transcript expression profiling. The number of binding sites per transcript, degree of HuR association, and degree of HuR-dependent RNA stabilization were positively correlated. Pre-mRNA and mature mRNA containing both intronic and 3' UTR binding sites were more highly stabilized than transcripts with only 3' UTR or only intronic binding sites, suggesting that HuR couples pre-mRNA processing with mature mRNA stability. We also observed HuR-dependent splicing changes and substantial binding of HuR in polypyrimidine tracts of pre-mRNAs. Comparison of the spatial patterns surrounding HuR and miRNA binding sites provided functional evidence for HuR-dependent antagonism of proximal miRNA-mediated repression. We conclude that HuR coordinates gene expression outcomes at multiple interconnected steps of RNA processing.
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Neelanjan
authors: N
authors: Mukherjee
authors: David L
authors: DL
authors: Corcoran
authors: Jeffrey D
authors: JD
authors: Nusbaum
authors: David W
authors: DW
authors: Reid
authors: Stoyan
authors: S
authors: Georgiev
authors: Markus
authors: M
authors: Hafner
authors: Manuel
authors: M
authors: Ascano
authors: Thomas
authors: T
authors: Tuschl
authors: Uwe
authors: U
authors: Ohler
authors: Jack D
authors: JD
authors: Keene
mesh_terms: D020816:Amino Acid Motifs; D000954:Antigens, Surface / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D001665:Binding Sites; D019295:Computational Biology; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology; D012322:RNA Precursors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D012984:Software
chemical_list: D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D035683:MicroRNAs; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins