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

Author

Listed:
  • 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
    Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH)

  • Myriam Gorospe

    (Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH)

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.

Suggested Citation

  • 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, 2014. "PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity," Nature Communications, Nature, vol. 5(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6248
    DOI: 10.1038/ncomms6248
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