Transcriptomics

Dataset Information

86

Global Target mRNA Specification and Regulation by RNA-Binding Protein ZFP36/Tristetraprolin/TTP [PAR-CLIP]


ABSTRACT: Tristetraprolin/ZFP36/TTP and ELAVL1/HuR are two disease-relevant RNA-binding proteins (RBPs) that both interact with AU-rich sequences but have antagonistic roles. While ELAVL1 binding has been profiled in several studies, the precise in vivo binding specificity of ZFP36 has not been investigated on a global scale. We determined ZFP36 binding preferences using cross-linking and immunoprecipitation in human embyonic kidney cells and examined combinatorial regulation of AU-rich elements by ZFP36 and ELAVL1. Among the targets ZFP36 binds and negatively regulates the mRNA of genes encoding proteins necessary for immune function and cancer, and other RBPs. Using partial correlation analysis, we were able to quantify the association between ZFP36 binding sites and differential target RNA abundance from ZFP36 overexpression independent of effects from confounding features, such as 3’ UTR length. We identified thousands of overlapping ZFP36 and ELAVL1 binding sites, in 1,313 genes. ZFP36 preferentially interacts with and regulates AU-rich sequences while ELAVL1 prefers predominantly U- and CU-rich sequences. RNA target specificity identified by global in vivo ZFP36-mRNA interactions were quantitatively similar to previously reported in vitro binding affinities. ZFP36 and ELAVL1 both bind an overlapping spectrum of RNA sequences, yet with differential relative preferences that dictate combinatorial regulatory potential. Our findings and methodology delineate an approach to untangle the in vivo combinatorial regulation by RNA-binding proteins. FLAG-HA ZFP36

ORGANISM(S): Homo sapiens  

SUBMITTER: Thomas Tuschl  Neelanjan Mukherjee   Perry J Blackshear   Uwe Ohler    

PROVIDER: E-GEOD-53184 | ArrayExpress | 2014-04-15

SECONDARY ACCESSION(S): SRP033656GSE53184PRJNA231063

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Global target mRNA specification and regulation by the RNA-binding protein ZFP36.

Mukherjee Neelanjan N   Jacobs Nicholas C NC   Hafner Markus M   Kennington Elizabeth A EA   Nusbaum Jeffrey D JD   Tuschl Thomas T   Blackshear Perry J PJ   Ohler Uwe U  

Genome biology 20140108 1


ZFP36, also known as tristetraprolin or TTP, and ELAVL1, also known as HuR, are two disease-relevant RNA-binding proteins (RBPs) that both interact with AU-rich sequences but have antagonistic roles. While ELAVL1 binding has been profiled in several studies, the precise in vivo binding specificity of ZFP36 has not been investigated on a global scale. We determined ZFP36 binding preferences using cross-linking and immunoprecipitation in human embryonic kidney cells, and examined the combinatorial  ...[more]

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