Identification of a Signature Motif in Target mRNAs of RNA-binding Protein AUF1

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Identification of a Signature Motif in Target mRNAs of RNA-binding Protein AUF1

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dc.contributor.author Mazan-Mamczarz, Krystyna
dc.contributor.author Kuwano, Yuki
dc.contributor.author Zhan, Ming
dc.contributor.author Gorospe, Myriam
dc.contributor.author White, Elizabeth
dc.contributor.author Martindale, Jennifer
dc.contributor.author Lal, Ashish
dc.date.accessioned 2010-12-10T14:52:34Z
dc.date.issued 2009
dc.identifier.citation Mazan-Mamczarz, Krystyna, Yuki Kuwano, Ming Zhan, Elizabeth J. White, Jennifer L. Martindale, Ashish Lal, and Myriam Gorospe. 2009. Identification of a signature motif in target mRNAs of RNA-binding protein AUF1. Nucleic Acids Research 37(1): 204-214. en_US
dc.identifier.issn 0305-1048 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4621990
dc.description.abstract The ubiquitous RNA-binding protein AUF1 promotes the degradation of some target mRNAs, but increases the stability and translation of other targets. Here, we isolated AUF1-associated mRNAs by immunoprecipitation of (AUF1–RNA) ribonucleoprotein (RNP) complexes from HeLa cells, identified them using microarrays, and used them to elucidate a signature motif shared among AUF1 target transcripts. The predicted AUF1 motif (29–39 nucleotides) contained 79% As and Us, consistent with the AU-rich sequences of reported AUF1 targets. Importantly, 10 out of 15 previously reported AUF1 target mRNAs contained the AUF1 motif. The predicted interactions between AUF1 and target mRNAs were recapitulated in vitro using biotinylated RNAs. Interestingly, further validation of predicted AUF1 target transcripts revealed that AUF1 associates with both the pre-mRNA and the mature mRNA forms. The consequences of AUF1 binding to 10 predicted target mRNAs were tested by silencing AUF1, which elevated the steady-state levels of only four mRNAs, and by overexpressing AUF1, which also lowered the levels of only four mRNAs. In total, we have identified a signature motif in AUF1 target mRNAs, have found that AUF1 also associates with the corresponding pre-mRNAs, and have discovered that altering AUF1 levels alone only modifies the levels of subsets of target mRNAs. en_US
dc.language.iso en_US en_US
dc.publisher Oxford University Press en_US
dc.relation.isversionof doi:10.1093/nar/gkn929 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615618/pdf/ en_US
dash.license LAA
dc.title Identification of a Signature Motif in Target mRNAs of RNA-binding Protein AUF1 en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Nucleic Acids Research en_US
dash.depositing.author Lal, Ashish
dc.date.available 2010-12-10T14:52:34Z
dash.affiliation.other HMS^Pediatrics-Children's Hospital en_US

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