HuR mRNA ligands expressed after seizure.
HuR is a ubiquitously expressed AU-rich element (ARE)-binding protein that interacts with and stabilizes selective early response gene (ERG) mRNAs after cell activation or stress. To date, approximately 20 mRNAs have been unambiguously defined as HuR ligands. Given the discordance between the large number of ERG mRNAs and those few defined as ligands, we applied in vitro selection to isolate a broad range of HuR mRNA ligands using postseizure mouse hippocampal tissue. Selected mRNAs were converted into cDNA libraries and sequenced. Using this approach, we have identified over 600 novel, putative HuR mRNA ligands. These genes code for a variety of proteins, including transcription factors, signaling molecules, and kinases, but many have unknown function. Consistent with the means of their selection, several of these HuR ligands are differentially expressed in hippocampus after seizure. These results demonstrate a biochemical approach to identify and characterize the diverse repertoire of ligands for HuR and other regulatory mRNA-binding proteins.
Westmark
Cara J
CJ
Department of Pathology and Laboratory Medicine, Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, Wisconsin 53705, USA.
Gourronc
Françoise A
FA
Bartleson
Virginia B
VB
Sayin
Umit
U
Bhattacharya
Saswati
S
Sutula
Tom
T
Malter
James S
JS
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D003292:Convulsants; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D015723:Gene Library; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010433:Pentylenetetrazole; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D000954:Antigens, Surface; D003292:Convulsants; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D008024:Ligands; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D010433:Pentylenetetrazole