The perinucleolar compartment (PNC) is a unique nuclear structure whose formation is correlated with the malignant phenotype both in cultured cells and in human cancer. Our long term objective is to understand the function of the PNC and its significance in the development and maintenance of the malignant phenotype. We will begin by addressing three problems. 1) What are the functional events that take place in the PNC? We have recently shown that the PNC incorporates labeled nucleotides within a short period of time, suggesting its involvement in RNA metabolism. We will clarify whether the incorporation represents transcription, or the post-transcriptional modification of RNA, or a combination of both, by analyzing the sequences where the labeled nucleotides are inserted, by determining whether the PNC is associated with chromosome and/or specific genes, and by examining the presence of transcription factors and RNA processing factors in the PNC. 2) What are the mechanisms that induce the formation of the PNC? We have found that the integrity of the PNC is influenced by the transcriptional state of the cells. We will experimentally change the level of rRNA and/or some of the pol III gene expression, and thereby examine the potential coordination between the activities of the two polymerases and their effect on the prevalence of the PNC. 3) What are the molecular constituents of the PNC? We will isolate and identify additional proteins and RNAs that are part of the PNC, thus generating more information with which we will search for factors that are responsible for the formation of the PNC and its function. The results of these experiments will provide an important foundation to address the significance of the PNC in malignant cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA077560-05
Application #
6628145
Study Section
Pathology B Study Section (PTHB)
Program Officer
Sussman, Daniel J
Project Start
1999-04-01
Project End
2005-01-31
Budget Start
2003-02-01
Budget End
2005-01-31
Support Year
5
Fiscal Year
2003
Total Cost
$217,567
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
Norton, John T; Huang, Sui (2013) The perinucleolar compartment: RNA metabolism and cancer. Cancer Treat Res 158:139-52
Kopp, K; Gasiorowski, J Z; Chen, D et al. (2007) Pol I transcription and pre-rRNA processing are coordinated in a transcription-dependent manner in mammalian cells. Mol Biol Cell 18:394-403
Kopp, K; Huang, S (2005) Perinucleolar compartment and transformation. J Cell Biochem 95:217-25
Chen, Danyang; Dundr, Miroslav; Wang, Chen et al. (2005) Condensed mitotic chromatin is accessible to transcription factors and chromatin structural proteins. J Cell Biol 168:41-54
Leary, Daniel J; Terns, Michael P; Huang, Sui (2004) Components of U3 snoRNA-containing complexes shuttle between nuclei and the cytoplasm and differentially localize in nucleoli: implications for assembly and function. Mol Biol Cell 15:281-93
Chen, Danyang; Belmont, Andrew S; Huang, Sui (2004) Upstream binding factor association induces large-scale chromatin decondensation. Proc Natl Acad Sci U S A 101:15106-11
Wang, Chen; Politz, Joan C; Pederson, Thoru et al. (2003) RNA polymerase III transcripts and the PTB protein are essential for the integrity of the perinucleolar compartment. Mol Biol Cell 14:2425-35
Spann, Timothy P; Goldman, Anne E; Wang, Chen et al. (2002) Alteration of nuclear lamin organization inhibits RNA polymerase II-dependent transcription. J Cell Biol 156:603-8
Chen, Danyang; Hinkley, Craig S; Henry, R William et al. (2002) TBP dynamics in living human cells: constitutive association of TBP with mitotic chromosomes. Mol Biol Cell 13:276-84
Pendergrast, P Shannon; Wang, Chen; Hernandez, Nouria et al. (2002) FBI-1 can stimulate HIV-1 Tat activity and is targeted to a novel subnuclear domain that includes the Tat-P-TEFb-containing nuclear speckles. Mol Biol Cell 13:915-29

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