Our long-term goal is to understand the structure and function of the PNC and its roles in malignancy. The perinucleolar compartment (PNC) is a multicomponent non-membrane bound nuclear substructure that localizes to the nucleolar periphery. We have found it to be unique to malignant transformation both in vitro and in vivo. The PNC is enriched with RNA newly synthesized by pol III and RNA binding proteins primarily implicated in pol II RNA processing. Our preliminary findings show that the PNC-associated RNAs are in the same complexes with some of the known pol II RNA binding proteins. These novel complexes are not restricted to the PNC since PTB-MRP RNA interactions can also be detected in normal cells without PNCs. However, the levels or the regulations of these complexes may change during malignancy, leading to the nucleation of these complexes in the PNC. These findings lead to our working model in which the PNC is associated with and may represent changes in novel molecular complexes that are involved in the metabolism of newly synthesized pol III RNA during malignancy. The goal of this proposal is to begin test this hypothesis by identifying and initially characterizing these novel RNPs, using RNase MRP RNA (one of the bona fide components of the PNC) as the first example, and by beginning to address the functional association of these RNPs with the PNC using cell biological approaches. As little is understood regarding the post-transcriptional processing and regulation of the pol III small non-coding RNAs, the solution of the novel RNPs is not only important for the understanding of PNC structure and function, but should also reveal a novel mechanism involved in the post-transcriptional regulation of these functional RNAs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM078555-04
Application #
7846780
Study Section
Nuclear Dynamics and Transport (NDT)
Program Officer
Carter, Anthony D
Project Start
2007-08-10
Project End
2012-04-30
Budget Start
2010-06-01
Budget End
2012-04-30
Support Year
4
Fiscal Year
2010
Total Cost
$282,226
Indirect Cost
Name
Northwestern University at Chicago
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Wang, Chen; Huang, Sui (2017) Drug Development Against Metastatic Cancers. Yale J Biol Med 90:119-123
Liu, Yanning; Lou, Guohua; Norton, John T et al. (2017) 6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib. FASEB J 31:5453-5465
Kim, Dong-Hyun; Li, Weiguo; Chen, Jeane et al. (2016) Multimodal Imaging of Nanocomposite Microspheres for Transcatheter Intra-Arterial Drug Delivery to Liver Tumors. Sci Rep 6:29653
Kuramoto, Kenta; Wang, Nan; Fan, Yuying et al. (2016) Autophagy activation by novel inducers prevents BECN2-mediated drug tolerance to cannabinoids. Autophagy 12:1460-71
Wang, Chen; Huang, Sui (2014) Nuclear function of Alus. Nucleus 5:131-7
Wen, Yiping; Wang, Chen; Huang, Sui (2013) The perinucleolar compartment associates with malignancy. Front Biol (Beijing) 8:
Norton, John T; Huang, Sui (2013) The perinucleolar compartment: RNA metabolism and cancer. Cancer Treat Res 158:139-52
Fitzpatrick, Terry; Huang, Sui (2012) 3'-UTR-located inverted Alu repeats facilitate mRNA translational repression and stress granule accumulation. Nucleus 3:359-69
Liu, Yanning; Norton, John T; Witschi, Mark A et al. (2011) Methoxyethylamino-numonafide is an efficacious and minimally toxic amonafide derivative in murine models of human cancer. Neoplasia 13:453-60
Pollock, Callie; Daily, Kelly; Nguyen, Van Trung et al. (2011) Characterization of MRP RNA-protein interactions within the perinucleolar compartment. Mol Biol Cell 22:858-67

Showing the most recent 10 out of 16 publications