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 TuschlNicholas T. Ingolia, Markus Hafner, Myriam Gorospe

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number5248
JournalNature communications
Volume5
DOIs
StatePublished - Jan 1 2014

Fingerprint

Ribonucleosides
genome
crosslinking
Immunoprecipitation
Crosslinking
integrity
Genes
Genome
RNA
RNA-Binding Proteins
Messenger RNA
Long Noncoding RNA
Untranslated RNA
Cell Aging
Protein Biosynthesis
Ribosomes
Gene expression
proteins
Aging of materials
Maintenance

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Yoon, J. H., De, S., Srikantan, S., Abdelmohsen, K., Grammatikakis, I., Kim, J., ... Gorospe, M. (2014). PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity. Nature communications, 5, [5248]. https://doi.org/10.1038/ncomms6248

PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity. / Yoon, Je Hyun; De, Supriyo; Srikantan, Subramanya; Abdelmohsen, Kotb; Grammatikakis, Ioannis; Kim, Jiyoung; Kim, Kyoung Mi; Noh, Ji Heon; White, Elizabeth J.F.; Martindale, Jennifer L.; Yang, Xiaoling; Kang, Min Ju; Wood, William H.; Noren Hooten, Nicole; Evans, Michele K.; Becker, Kevin G.; Tripathi, Vidisha; Prasanth, Kannanganattu V.; Wilson, Gerald M.; Tuschl, Thomas; Ingolia, Nicholas T.; Hafner, Markus; Gorospe, Myriam.

In: Nature communications, Vol. 5, 5248, 01.01.2014.

Research output: Contribution to journalArticle

Yoon, JH, De, S, Srikantan, S, Abdelmohsen, K, Grammatikakis, I, Kim, J, Kim, KM, Noh, JH, White, EJF, Martindale, JL, Yang, X, Kang, MJ, Wood, WH, Noren Hooten, N, Evans, MK, Becker, KG, Tripathi, V, Prasanth, KV, Wilson, GM, Tuschl, T, Ingolia, NT, Hafner, M & Gorospe, M 2014, 'PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity', Nature communications, vol. 5, 5248. https://doi.org/10.1038/ncomms6248
Yoon JH, De S, Srikantan S, Abdelmohsen K, Grammatikakis I, Kim J et al. PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity. Nature communications. 2014 Jan 1;5. 5248. https://doi.org/10.1038/ncomms6248
Yoon, Je Hyun ; De, Supriyo ; Srikantan, Subramanya ; Abdelmohsen, Kotb ; Grammatikakis, Ioannis ; Kim, Jiyoung ; Kim, Kyoung Mi ; Noh, Ji Heon ; White, Elizabeth J.F. ; Martindale, Jennifer L. ; Yang, Xiaoling ; Kang, Min Ju ; Wood, William H. ; Noren Hooten, Nicole ; Evans, Michele K. ; Becker, Kevin G. ; Tripathi, Vidisha ; Prasanth, Kannanganattu V. ; Wilson, Gerald M. ; Tuschl, Thomas ; Ingolia, Nicholas T. ; Hafner, Markus ; Gorospe, Myriam. / PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity. In: Nature communications. 2014 ; Vol. 5.
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