Sui Huang
Title: Assistant Professor
Research area: Dynamics of Nuclear Organization
Degree: Ph.D., Rutgers University.
Voice: 312.503.4269
Fax: 312.503.7912
e-mail: s-huang2@northwestern .edu

Detailed research description:
The Structure and Function of the Perinucleolar Compartment

The main focus of our studies is to understand the nature and function of a unique nuclear structure, the perinucleolar compartment (PNC) and its relationship with the malignant phenotype. The PNC is an electron dense structure forming a reticulated mesh on the surface of the nucleolus. It is predominantly observed in transformed cells, and is rarely found in normal cells. Several small RNAs transcribed by RNA polymerase III and two hnRNP proteins have thus far been localized in this structure. The PNC intensely incorporates Br-U (a nucleotide analogue) in permeabilized cells after a short pulse labeling and a PNC-associated RNA binding protein, PTB, moves in and out of PNC rapidly. These observations suggest that the PNC is a dynamic and functional subnuclear compartment, which may be involved in transcription and/or RNA post-transcriptional processing in cancer cells. More recently, preliminary studies suggest that suppressing the function of an anti-oncogene (p53) significantly increases PNC prevalence (the percentage of cells that contain at least one PNC). These studies used cells stably transfected with a ts p53 mutant in a p53 -/- background. In addition, the integrity of the PNC is dependent upon RNA polymerase I activity, which is in part regulated by p53. These findings suggest that the high PNC prevalence in transformed cells may reflect the elevated level of rRNA synthesis in cancer cells.

We have proposed several approaches to address the function of the PNC and its significance during malignant transformation. 1), We will determine the correlation between PNCs and cancer in tissues. In collaboration with Dr. Ann Thor at Evanston Hospital, Northwestern University, we have initiated detection of PNC in breast cancer tissues. Preliminary finding reveals that the PNC is only found in invasive carcinomas or liver metastasis, and is not found in the normal breast tissue. We will soon begin a systematic evaluation of the correlation between the PNC prevalence and the degree of malignancy using breast cancer as a model system. The results of these experiments will not only assess the potential for the PNC to be a useful prognostic tumor marker, but will also reveal the biological relevance between the formation of the PNC and the development of the malignant phenotype. 2), We are investigating the function of the PNC, its relationship with the nucleolus and rRNA synthesis. We are in the process of isolating and identifying additional proteins and RNAs in the PNC. Recently, we found a 200 kd phosphorylated protein to be concentrated in both the nucleolus and the PNC. We hypothesize that p200 may physically and functionally link the PNC to the nucleolus. In addition, two of the small RNAs enriched in the PNC, RNAse P RNA and RNAse MRP RNAs, have been shown to be involved in rRNA processing. To determine whether these RNAs are transcribed, or processed, or assembled into RNPs, or are functioning in the PNC will help understand the roles that the PNC may play. We can exclude the possibility that these RNAs are transcribed there, since we have shown that the encoding genes are not localized to or near the PNC. We are currently analyzing the other possibilities listed above. Identification of activities taking place in the PNC will shed light on the understanding of the function of this structure and its relationship to the nucleolus and the transformed phenotype.


Representative publications:


D. J. Leary, M. P. Terns, and S. Huang. 2003. Components of U3 snoRNA Containing  Complexes Shuttle Between Nuclei and the Cytoplasm and  Differentially Localize in Nucleoli: Implications for  Assembly and Function, Mole. Biol. Cell. In press. 

R. Kamath, D. J. Leary, and S. Huang. 2003. Nuclear components  and tumor markers. Visions of the Nucleus-Eukaryotic DNA.   American Scientific Publishers. Stevenson Ranch, California. USA. 

C. Wang, J. C. Politz, T. Pederson and S. Huang. 2003. Pol III RNAs and PTB Protein are Essential for the Integrity of Perinucleolar Compartments.  Mole. Biol. Cell. 14:2425- 2435. 

S. Huang. 2002. Building an efficient factory: Where is pre-rRNA synthesized in the nucleolus? J. Cell Biol. 157: 739-741.

P. S. Pendergrast, C. Wang, N. Hernandez, and S. Huang. 2002. FBI-1 can Stimulate HIV-1 Tat Activity and is Targeted to a Novel Sub-nuclear Domain that Includes the Tat-PTEFb-containing Nuclear Speckles.  Mole. Biol. Cell. 13: 915-929.

T. P. Spann, A. E. Goldman, C Wang, S. Huang, and R. D. Goldman. 2002. Alteration of  nuclear lamin organization inhibits RNA polymerase II–dependent transcription. J. Cell Biol. 156: 603-608. 

D. Chen, C. Hinkley, R. W., Henry, and S. Huang. 2002. TBP dynamics in living human cells: constitutive association of TBP with mitotic chromosomes.  Mol. Biol. Cell 13: 276-284. 

D. J. Leary, and S. Huang. 2001. Regulation of ribosome biogenesis within the nucleolus. FASEB L. 509: 145-150. 

R. V. Kamath, D. J., Leary, and S., Huang. 2001. Nucleocytoplasmic Shuttling of  Polypyrimidine Tract-Binding Protein is Uncoupled from RNA Export.  Mol. Biol. Cell 12:3808-3820. 

D.Chen, and S. Huang. 2001.  Nucleolar components involved in       ribosome biogenesis cycle between the nucleolus and nucleoplasm in interphase cells.  J. Cell Biol. 153: 169-176.

T. Dousset, C. Wang, C. Verheggen, D-Y. Chen, D. Hernandez-Verdun, and S. Huang. 2000. Initiation of Nucleolar Assembly is Independent of RNA Polymerase I Transcription.  Mole. Biol. Cell.  11: 2705-2717.

Huang, S. 2000. The perinucleolar structures. J. Struct. Biol. 129: 233-240.

 

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