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
Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, Maryland 21224, USA.
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Nat Commun. 2014 Nov 4;5:5248. doi: 10.1038/ncomms6248.
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.
转录后基因调控受到RNA结合蛋白（RBPs）的严格调控。在此，我们描述了受AUF1（AU结合因子1）调控的RNA集合，AUF1是一种与癌症、炎症和衰老相关的RBP。光活化核糖核苷增强交联和免疫沉淀（PAR-CLIP）分析表明，AUF1主要识别mRNA和非编码RNA中富含U-/GU的序列，并在三个主要方向上影响靶转录本的命运。首先，AUF1降低了许多靶RNA的稳态水平，包括长链非编码RNA NEAT1，进而影响核旁斑的组织。其次，AUF1不会改变许多靶RNA的丰度，但核糖体谱分析表明，AUF1促进了该组中许多mRNA的翻译。第三，AUF1意外地提高了几种编码DNA维持蛋白的靶mRNA的稳态水平。通过对靶RNA的作用，AUF1保持了基因组完整性，这与AUF1诱导的预防细胞早衰一致。
