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

Je-Hyun Yoon (), Supriyo De, Subramanya Srikantan, Kotb Abdelmohsen, Ioannis Grammatikakis, Jiyoung Kim, Kyoung Mi Kim, Ji Heon Noh, Elizabeth J. F. White, Jennifer L. Martindale, Xiaoling Yang, Min-Ju Kang, William H. Wood, Nicole Noren Hooten, Michele K. Evans, Kevin G. Becker, Vidisha Tripathi, Kannanganattu V. Prasanth, Gerald M. Wilson, Thomas Tuschl, Nicholas T. Ingolia, Markus Hafner and Myriam Gorospe ()
Additional contact information
Je-Hyun Yoon: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
Supriyo De: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
Subramanya Srikantan: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
Kotb Abdelmohsen: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
Ioannis Grammatikakis: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
Jiyoung Kim: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
Kyoung Mi Kim: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
Ji Heon Noh: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
Elizabeth J. F. White: University of Maryland School of Medicine
Jennifer L. Martindale: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
Xiaoling Yang: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
Min-Ju Kang: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
William H. Wood: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
Nicole Noren Hooten: Laboratory of Epidemiology and Population Sciences, National Institute on Aging-Intramural Research Program, NIH
Michele K. Evans: Laboratory of Epidemiology and Population Sciences, National Institute on Aging-Intramural Research Program, NIH
Kevin G. Becker: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH
Vidisha Tripathi: University of Illinois at Urbana-Champaign
Kannanganattu V. Prasanth: University of Illinois at Urbana-Champaign
Gerald M. Wilson: University of Maryland School of Medicine
Thomas Tuschl: Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, Rockefeller University
Nicholas T. Ingolia: Carnegie Institution for Science
Markus Hafner: Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, Rockefeller University
Myriam Gorospe: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6248

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