A novel nuclear structure containing the survival of motor neuron protein / Qing Liu.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Liu, Qing.

Contributor:

Dreyfuss, Gideon, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Biology.

Biology--Penn dissertations.

Biology.

Academic Dissertations as Topic.

Medical Subjects:

Biology.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Biology.

Biology--Penn dissertations.

Physical Description:

x, 107 pages : illustrations ; 29 cm

Production:

1996.

Summary:

HnRNP proteins are a group of abundant nuclear proteins that bind pre-mRNAs and nuclear mRNAs and play important roles in the processing and transport of mRNAs. Many of the hnRNP proteins undergo extensive post-translational modifications including methylation on arginine residues. HnRNP proteins contain about 65% of the total $N\sp{G},\ N\sp{G}$-dimethylarginine found in the cell nucleus. The role of this modification is unknown. Using biochemical approaches, the first part of this work reports studies on the partial purification of the arginine-specific methyltransferase activity, and the characterization of this enzyme, and addresses the effect of methylation on the hnRNP proteins activity. These studies show that the majority of the hnRNP proteins are methylated in vivo on arginine residues within the RGG box domain. This methylation is a very stable modification and it results in reduced binding of the hnRNP proteins to RNA.

The second part of this work describes the discovery of a novel nuclear structure termed gemini of coiled bodies (gems). This structure was discovered during characterization of the protein product of the survival of the motor neuron (SMN) gene. SMN is most likely to be the cause of the common genetic disease, Spinal Muscular Atrophy (SMA). Using biochemical and cell biological approaches, I found that the SMN protein localizes in a unique subnuclear structure. Only very few structures of specific morphology and composition have been defined in the nucleus. These are nucleoli, coiled bodies, perichromatin fibrils, perichromatin granules and the interchromatin granules. Besides the nucleolus, which are the sites of rRNA biogenesis, the function of these subnuclear structures remains unclear. The structures containing the SMN protein are different from those mentioned above but closely associated with coiled bodies, both physically and functionally. Thus we named them gemini of coiled bodies (gems). Studies of SMN also lead to the finding of another component of gems, SMN interacting protein I (SIP I). SIP I interacts with SMN both in vivo and in vitro. Besides SIP I, the SMN protein forms a complex with several other proteins, including a subset of snRNP proteins indicating that SMN probably functions in snRNP biogenesis. These studies provide important contributions to the understanding of the molecular basis of SMA and thus provide insight into the structure of the nucleus and the function of coiled bodies.

Notes:

Supervisor: Gideon Dreyfuss.

Thesis (Ph.D. in Biology) -- University of Pennsylvania, 1996.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 97-12966.

OCLC:

187469396