Mark O. J. Olson, Ph.D.

Ph.D.  from the University of Minnesota.

The long range goals of this research program are to understand how the nucleolus is formed from its individual components and how it assembles ribosomes. The nucleolus contains the biochemical machinery for synthesis and processing of preribosomal RNA and for its assembly into preribosomal particles. This process is achieved with the aid of nonribosomal nucleolar proteins whose roles are poorly understood.  In the past several years, we have focused on two of these, called B23 and nucleolin, which have multiple functions in ribosome biogenesis. Both are acidic phosphoproteins associated with nucleolar preribosomal RNP particles.  Nucleolin is a RNA binding protein which is bound to newly synthesized preribosomal RNA.  Protein B23 (also called NO38, nucleophosmin or NPM) binds both RNA and DNA, and it has ribonuclease activity, suggesting that it plays a direct role in preribosomal RNA processing.  Protein B23 also binds the HIV-1 Rev protein and stimulates its import into the nucleus.  Finally, protein B23 is a molecular chaperone, which  may facilitate the ribosome assembly process.   The chaperone activity seems to be regulated by phosphorylation by protein kinase CK2 (Szebeni et al., 2003).

An outgrowth of the work on the molecular chaperone activity of protein B23 has been a biotechnology project focusing on the use of this activity for enhancing the thermostability of proteins, renaturing denatured proteins and preventing inclusion body formation by recombinant proteins expressed in bacteria.  A patent for these applications was issued in 2002 (see below).

Another area of emphasis is concerned with the location of nucleolar components during mitosis and how they are assembled into the reforming nucleolus at the end of mitosis. Preribosomal RNA  transcription and processing are shut down during mitosis. Consequently, partially processed preribosomal RNA is preserved in association with processing components in large particles called nucleolus derived foci (NDF) during anaphase and telophase.  In telophase, the NDF along with the peripheral regions of chromosomes provide material for the formation of prenucleolar bodies (PNBs), which in turn,  feed components into newly-forming postmitotic nucleoli.  This process utilizes pre-assembled RNA-protein complexes, whose subcomponents are released to the nucleoli in a defined order.  The dynamics of nucleologenesis was recently demonstrated by time-lapse  fluorescence microscopy of living cells expressing green fluorescent protein fusions with nucleolar proteins (Dundr et al., 2000).  Three movies showing how these proteins behave during telophase may be downloaded as indicated below. 

Recent Publications

Szebeni, A., Mehrotra, B., Baumann, A., Wingfield, P. and Olson, M.O.J. Nucleolar protein B23 stimulates nuclear import of NLS-conjugated bovine albumin and the HIV-1 Rev protein. Biochemistry 36: 3941-3949, 1997. 

Savkur, R., and Olson, M.O.J.  Preferential cleavage in pre-ribosomal RNA by  protein B23 endoribonuclease. Nucleic Acids Res.26: 4508-4515, 1998. 

Dundr, M. and Olson, M.O.J.  Partially processed preribosomal RNA is preserved in association with processing components in nucleolus-derived foci during mitosis. Mol. Biol. Cell 9:2407-2422, 1998. 

Szebeni, A. and Olson, M.O.J.  Nucleolar protein B23 has molecular chaperone activity. Protein Science 8:905-912,1999.

Olson, M.O.J., Dundr, M. and Szebeni, A. The nucleolus: an old factory with unexpected capabilities. Trends in Cell Biology 10:189-196, 2000.

Hingorani, K., Szebeni, A. and Olson, M.O.J. Mapping the functional domains of nucleolar protein B23. J. Biol. Chem.275: 24451-24457, 2000.

Dundr, M., Misteli, T. and Olson, M.O.J. The dynamics of postmitotic re-assembly of the nucleolus. J. Cell. Biol.150: 433-446, 2000.

Olson, M.O.J., Hingorani, K. and Szebeni, A. Conventional and nonconventional roles of the nucleolus. Int. Rev. Cytol. 219: 199-266, 2002.

Szebeni, A., Hingorani, K.,  Negi, S. and Olson, M.O.J. Role of protein kinase  CK2 in the molecular chaperone activity of  nucleolar protein B23. J. Biol. Chem.  In press, 2003.

Patent:

Olson, M.O.J. and Szebeni, A.  Methods for stabilization and renaturation of proteins using nucleolar protein B23.  Patent # 6,358,718, issued March 19, 2002.