Yang Zhang

Defense Date

3-18-2014

Graduation Date

2014

Availability

Immediate Access

Submission Type

thesis

Degree Name

MS

Department

Pharmaceutics

School

School of Pharmacy

Committee Chair

Mihaela-Rita Mihailescu

Committee Member

James Drennen

Committee Member

Wilson Meng

Keywords

FMRP, Fragile X syndrome, G-quadruplex, RNA

Abstract

Fragile X syndrome (FXS), the most common cause of inherited mental impairment, is caused by the loss of expression of the fragile X mental retardation protein (FMRP). As an RNA binding protein, FMRP has been proposed to regulate the transport and translation of specific message RNA (mRNA). It has been reported that FMRP uses its RGG box domain to bind mRNA targets that form a G-quadruplex structure, structure believed to be important for FMRP recognition of at least a subclass of its mRNA targets. We have hypothesized that the interaction of FMRP with selected relevant mRNA targets occurs in a G-quadruplex dependent manner. By analyzing the structure of two FMRP in vivo mRNA targets, Shank1 mRNA and BASP1 mRNA, and their interactions with FMRP, we showed a high-affinity interaction between Shank1 RNA G-quadruplex and FMRP. The other G-quadruplex forming mRNA BASP1, however, interacts with FMRP using other structural elements.

Format

PDF

Language

English

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