Skip to Main Content
 

Global Search Box

 
 
 
 

ETD Abstract Container

Abstract Header

A Functional Analysis of the Small Nuclear RNP Import Adaptor, Snurportin1

Ospina, Jason Kerr

Abstract Details

2005, Doctor of Philosophy, Case Western Reserve University, Genetics.
Cells are the fundamental units of life and are therefore intimately connected to life’s vitality. Crucial to cellular function is an ability to coordinate and regulate numerous intricate processes. The generation of spliceosomal uridine-rich small nuclear ribonucleoproteins (U snRNPs) is a fascinating example, as it requires both cytoplasmic and nuclear phases. The generation of snRNPs begins in the nucleus with the transcription of snRNAs. Nascent snRNAs are then exported to the cytoplasm where maturation results in newly assembled snRNP particles. A subset of these cytoplasmic steps requires the survival of motor neurons (SMN) protein complex. Resulting particles are imported back into the nucleus, where they are further modified. Mature snRNPs are then incorporated into the spliceosome and play a vital role in pre-mRNA splicing. Central to snRNP biogenesis is the proper targeting of precursor molecules. As snRNPs are processed in the cytoplasm, but function in the nucleus, import factors are required to transport these components across the nuclear envelope. Import is directed by two independent signals found on snRNPs. One import signal consists of a 5' RNA cap structure and is bound by the transport adaptor, snurportin1 (SPN). The precise identity of the other transport adaptor remains elusive, however it’s activity lies within the SMN complex. I have utilized both in vitro and in vivo approaches to study the process of U snRNP import. This thesis has identified a pre-import complex containing SPN, SMN and the transport receptor, importin β. This work also provides significant insight into the function of SPN-mediated snRNP import. Residues required for SPN function have been identified and validated by functional studies. The utilization of mutants deficient in function illustrates that cargo is not a prerequisite for SPN import. The binding of SPN to its export receptor exportin1, is disrupted by the drug leptomycin B, resulting in the accumulation of SPN in Cajal bodies. Finally, a novel interaction between the N- and C-termini of SPN was uncovered, indicating the possibility of an intramolecular regulation of snRNP import.
A. Matera (Advisor)
217 p.

Recommended Citations

Citations

  • Ospina, J. K. (2005). A Functional Analysis of the Small Nuclear RNP Import Adaptor, Snurportin1 [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1121703058

    APA Style (7th edition)

  • Ospina, Jason. A Functional Analysis of the Small Nuclear RNP Import Adaptor, Snurportin1. 2005. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1121703058.

    MLA Style (8th edition)

  • Ospina, Jason. "A Functional Analysis of the Small Nuclear RNP Import Adaptor, Snurportin1." Doctoral dissertation, Case Western Reserve University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=case1121703058

    Chicago Manual of Style (17th edition)