Identification of a Signature Motif in Target mRNAs of RNA-binding Protein AUF1
View/ Open
Author
Mazan-Mamczarz, Krystyna
Kuwano, Yuki
Zhan, Ming
Gorospe, Myriam
Published Version
https://doi.org/10.1093/nar/gkn929Metadata
Show full item recordCitation
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.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615618/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:4621990
Collections
- HMS Scholarly Articles [17917]
Contact administrator regarding this item (to report mistakes or request changes)