Ho-Hyung Woo, PhD

Laboratory of RNA-Protein Interactions

E-Mail Address: 
hwoo@uacc.arizona.edu
Short Bio: 
Dr. Woo received his PhD from the University of Minnesota, Twin Cities, and his undergraduate degree from the Korea University, Seoul, Korea. He did postdoctoral work at the Memorial Sloan-Kettering Cancer Center, New York.
 
His research goal is to understand the molecular mechanisms of mRNA translation. He is interested particularly in how RNA-binding proteins are involved in translational regulation.
 
His current research focuses on the molecular basis of metastasis in epithelial ovarian and breast cancers. Abnormal expression of proto-oncogenes c-fms and CSF-1 is an important prognostic factor. CSF-1 encodes colony stimulating factor-1 (CSF-1) and c-fms encodes receptor tyrosine kinase, a sole receptor to CSF-1. His research focuses on post-transcriptional and translational regulation of c-fms and CSF-1 by means of RNA-binding proteins, miRNAs and their interactions with mRNA untranslated regions.
 
 
 
Research Information
Summary of Research Activity: 
 
Translation Repression
In post-transcriptional regulation of mRNAs, RNA binding proteins (RBP) are important trans-acting regulators. RBPs work either as activator or repressor of translation. We are particulary interested in repressor loop formation by RBPs during translation repression. RBP vigilin is a repressor for c-fms mRNA translation and may be involved in reperssor loop formation.
 
Our research indicates that both Vigilin and HuR work together to coordinate the translation of c-fms mRNA. Dysregulation of coordination between Vigilin and HuR can cause abnormal expression of c-fms mRNA.
 
 
Translation-7 copy.jpg 
 
 
 
Deadenylation and Bulk Translation
Deadenylation is generally thought the first step following decapping and exonuclease digestion in mRNA decay.  However, deadenylation may have another unidentified function for bulk translation.  After pioneer translation of mRNA associated with nuclear CBC at the 5’-cap, canonical mRNP closed-loop is formed by joining 5’- and 3’-ends of mRNA for bulk translation. The cap-dependent mRNP closed-loop is formed by binding of PABPC both to the poly(A)n tail at the 3’UTR and eIF4G of the translation initiation complex at the 5’-cap. In contrast, PABPC is also involved in miRNA-directed mRNA decay by attracting deadenylase complex. Importantly, we documented that nucleolin has similar function like PABPC; i.e., nucleolin induces miRNA-directed deadenylation, but increases translation of CSF-1 mRNA. Nucleolin interacts to the Pan2 and Pan3 of deadenylase complex, but not to the CCR4-NOT, indicating nucleolin’s involvement in early stage of deadenylation. Nucleolin also interacts to the eIF4F translation initiation complex. We found that deadenylated mRNAs are still associated with polysomes in nucleolin overexpressed cell lines. Together these results indicate that removal of poly(A)n tail is not always followed by mRNA decay, but can enhance bulk translation. Nucleolin binds dsRNA structure. For example, in p53 mRNA, nucleolin stabilizes the dsRNA formed by the mRNA 5’- and 3’-UTR complementary sequence interaction resulting non-canonical closed-loop lacking poly(A)n tail. Ribosomal protein RpL26 replaces nucleolin and binds dsRNA, and stimulates bulk translation. Nucleolin may play as a mediator for the transition from canonical to non-canonical closed-loop for bulk translation. Binding of nucleolin to the dsRNA can enhance deadenylation and non-canonical closed-loop formation.
 
Nucleolin consists of three domains including acidic stretches, RRM for RNA binding, and RGG motif. Overexpression of RRM domain alone increases both CSF-1 mRNA and protein levels. In contrast, overexpression of either acidic or RGG domain alone decreases CSF-1 protein level without affecting CSF-1 mRNA level.
 

Translation copy.jpg

 

Selected Publications: 
 
 
2013:
1.  Nucleolin mediates microRNA-directed CSF-1 mRNA deadenylation, but increases translation of CSF-1 mRNA. Molecular & Cellular Proteomics. 12: 1661-1677. (Cover paper)
 
2. Prevention of bone metastasis and bone destruction from breast cancer by autocrine inhibition of the c-fms proto-oncogene. Molecular Oncology.
 
3.  Post-transcriptional regulation of proto-oncogene c-fms by RNA binding proteins in breast cancer. Oncogene and Cancer. Chapter 13. pp295-316. 
 
 
2012:
4.  Regulation of colony stimulating factor-1 expression and ovarian cancer cell behavior in vitro by miR-128 and miR-152. Molecular Cancer. 11:58 doi:10.1186/1476-4598-11-58.
 
 
2011:
5.  Post-transcriptional suppression of proto-oncogene c-fms expression by vigilin in breast cancer. Molecular and Cellular Biology. 31: 215-225.
 
 
2010:
6.  Inhibition of the c-fms proto-oncogene autocrine loop and tumor phenotype in glucocorticoid stimulated human breast carcinoma cells. Breast Cancer Research and Treatment. 129: 411-419.
 
 
2009:
7.  Regulation of non-AU-rich element containing c-fms proto-oncogene expression by HuR in breast cancer.  Oncogene. 28: 1176-1186.

 

 

Professional Information
Professional Affiliations: 

1. American Society for Biochemistry and Molecular Biology

2. American Society for Microbiology

3. Associate Editor - European Journal of Molecular Biology

4. Technical Editor - VRI Cell Signaling

5. Technical Editor - VRI Biological Medicinal Chemistry

 

Academic Information
Doctorate: 
University of Minnesota, Twin Cities
Undergraduate School: 
Korea University, Seoul, Korea