This proposal by Dr. Shyu is a continuation of his work from the previous funding period. He has made significant progress and contributions to the understanding of ARE-mediated mRNA turnover and appears to have all the groundwork to continue to do so. The proposal investigates the role of hnRNP D (also known as AUF1) in the degradation of ARE-containing mRNAs and how post-translational modifications and associated proteins influence this activity.
The specific aims below are designed to obtain answers to the following questions: 1. What are the roles played by stress-activated signaling pathways and the ubiquitin-proteasome pathway in ARE-directed mRNA turnover? 2. What is the ARE/protein decay complex necessary for ARE-dependent mRNA turnover? 3. What structural features of hnRNP D are necessary for its role as a destabilizing protein in ARE-mediated mRNA decay in vivo? 4. How does the ARE exert its destabilizing function? The investigator proposes to address this question by employing in vitro RNA decay systems to dissect and characterize the ARE-targeted mRNA decay.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Cell Development and Function Integrated Review Group (CDF)
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Rhoades, Marcus M
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University of Texas Health Science Center Houston
Schools of Medicine
United States
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Chen, Chyi-Ying A; Zhang, Yueqiang; Xiang, Yu et al. (2017) Antagonistic actions of two human Pan3 isoforms on global mRNA turnover. RNA 23:1404-1418
Chen, Chyi-Ying A; Shyu, Ann-Bin (2017) Emerging Themes in Regulation of Global mRNA Turnover in cis. Trends Biochem Sci 42:16-27
Masamha, Chioniso P; Xia, Zheng; Peart, Natoya et al. (2016) CFIm25 regulates glutaminase alternative terminal exon definition to modulate miR-23 function. RNA 22:830-8
Chen, Chyi-Ying A; Chang, Jeffrey T; Ho, Yi-Fang et al. (2016) MiR-26 down-regulates TNF-?/NF-?B signalling and IL-6 expression by silencing HMGA1 and MALT1. Nucleic Acids Res 44:3772-87
Yoshikawa, Takeshi; Wu, Jianfeng; Otsuka, Motoyuki et al. (2015) ROCK inhibition enhances microRNA function by promoting deadenylation of targeted mRNAs via increasing PAIP2 expression. Nucleic Acids Res 43:7577-89
Shyu, Ann-Bin (2015) Study of mRNA turnover never decays. RNA 21:738-9
Chen, Chyi-Ying A; Shyu, Ann-Bin (2014) Emerging mechanisms of mRNP remodeling regulation. Wiley Interdiscip Rev RNA 5:713-22
Masamha, Chioniso P; Xia, Zheng; Yang, Jingxuan et al. (2014) CFIm25 links alternative polyadenylation to glioblastoma tumour suppression. Nature 510:412-6
Huang, Kai-Lieh; Chadee, Amanda B; Chen, Chyi-Ying A et al. (2013) Phosphorylation at intrinsically disordered regions of PAM2 motif-containing proteins modulates their interactions with PABPC1 and influences mRNA fate. RNA 19:295-305
Chen, Chyi-Ying A; Shyu, Ann-Bin (2013) Protein segregase meddles in remodeling of mRNA-protein complexes. Genes Dev 27:980-4

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