TY - JOUR
T1 - PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity
AU - Yoon, Je Hyun
AU - De, Supriyo
AU - Srikantan, Subramanya
AU - Abdelmohsen, Kotb
AU - Grammatikakis, Ioannis
AU - Kim, Jiyoung
AU - Kim, Kyoung Mi
AU - Noh, Ji Heon
AU - White, Elizabeth J.F.
AU - Martindale, Jennifer L.
AU - Yang, Xiaoling
AU - Kang, Min Ju
AU - Wood, William H.
AU - Noren Hooten, Nicole
AU - Evans, Michele K.
AU - Becker, Kevin G.
AU - Tripathi, Vidisha
AU - Prasanth, Kannanganattu V.
AU - Wilson, Gerald M.
AU - Tuschl, Thomas
AU - Ingolia, Nicholas T.
AU - Hafner, Markus
AU - Gorospe, Myriam
N1 - Funding Information:
We thank R.J. Schneider (NY University), H.Y. Chang (Stanford University), J.L. Rinn (Broad Institute), J.T. Lee and H. Sunwoo (Harvard Medical School), T. Hirose (National Institute of Advanced Industrial Science and Technology, Japan) and N. Mukherjee (Max Delbrück Center for Molecular Medicine, Germany) for providing reagents and information. J.-H.Y., S.S., S.D., I.G., M.-J.K., W.H.W., K.G.B., K.A., J.K., K.M.K., J.H.N., J.L.M., X.Y., N.N.H., M.K.E. and M.G. were supported by the NIA-IRP, NIH. E.J.F.W.
Funding Information:
and G.M.W. were supported by American Heart Association Grant 11PRE6900008 and NIH R01 CA102428. V.T. and K.V.P. were supported by NIH R01 GM088252. M.H. was supported by the Charles H. Revson Foundation and the NIAMS-IRP, NIH, and T.T. was supported by Howard Hughes Medical Institute (HHMI), the Starr Cancer Foundation and NIH. N.T.I. was supported by a Ruth L. Kirschstein National Research Service Award (GM080853) and the Searle Scholars Program.
Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84948614436&partnerID=8YFLogxK
U2 - 10.1038/ncomms6248
DO - 10.1038/ncomms6248
M3 - Article
C2 - 25366541
AN - SCOPUS:84948614436
SN - 2041-1723
VL - 5
JO - Nature communications
JF - Nature communications
M1 - 5248
ER -