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Nat Commun. 2014 Nov 4;5:5248. doi: 10.1038/ncomms6248.

PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity.

Author information

1
Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, Maryland 21224, USA.
2
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
3
Laboratory of Epidemiology and Population Sciences, National Institute on Aging-Intramural Research Program, NIH, Baltimore, Maryland 21224, USA.
4
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
5
Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, Rockefeller University, New York, New York 10065, USA.
6
Department of Embryology, Carnegie Institution for Science, Baltimore, Maryland 21218, USA.
7
1] Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, Rockefeller University, New York, New York 10065, USA [2] Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892, USA.

Abstract

Post-transcriptional gene regulation is robustly regulated by RNA-binding proteins (RBPs). Here we describe the collection of RNAs regulated by AUF1 (AU-binding factor 1), an RBP linked to cancer, inflammation and aging. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) analysis reveals that AUF1 primarily recognizes U-/GU-rich sequences in mRNAs and noncoding RNAs and influences target transcript fate in three main directions. First, AUF1 lowers the steady-state levels of numerous target RNAs, including long noncoding RNA NEAT1, in turn affecting the organization of nuclear paraspeckles. Second, AUF1 does not change the abundance of many target RNAs, but ribosome profiling reveals that AUF1 promotes the translation of numerous mRNAs in this group. Third, AUF1 unexpectedly enhances the steady-state levels of several target mRNAs encoding DNA-maintenance proteins. Through its actions on target RNAs, AUF1 preserves genomic integrity, in agreement with the AUF1-elicited prevention of premature cellular senescence.

PMID:
25366541
PMCID:
PMC4291169
DOI:
10.1038/ncomms6248
[Indexed for MEDLINE]
Free PMC Article

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