Lakshmi Menon

Defense Date

6-26-2008

Graduation Date

Summer 2008

Availability

Immediate Access

Submission Type

dissertation

Degree Name

PhD

Department

Chemistry and Biochemistry

Committee Chair

Mihaela Rita Mihailescu

Committee Member

Charles Dameron

Committee Member

Ellen Gawalt

Committee Member

Nancy Trun

Keywords

fragile X syndrome, RGG box, human semaphorin 3F RNA, fragile X mental retardation protein, G quadruplex RNA, microtubule associated 1B RNA

Abstract

The absence of fragile X mental retardation protein (FMRP) causes Fragile X Syndrome, the most common form of inherited mental retardation. FMRP, an RNA binding protein and, part of large ribonucleoprotein complexes, is proposed to participate in the transport, localization and translation regulation of specific target mRNAs. How the absence of this protein leads to mental retardation is not clearly understood. FMRP has been shown to use its Arginine-Glycine-Glycine (RGG) box to bind with high affinity to target RNA sequences containing G quadruplex structures. Two of the proposed mRNA targets of FMRP are the human semaphorin 3F (S3F) mRNA and the microtubule associated protein 1B (MAP1B) mRNA. The overall objective of this project is to understand the role played by the G quadruplex structure in the FMRP recognition of its mRNA targets. In this study, we demonstrate that S3F/MAP1B RNAs, fold into parallel intramolecular G quadruplex structures, to which the FMRP RGG box domain binds with high affinity and specificity. We also analyzed the interactions between the S3F/MAP1B RNA targets and the two autosomal paralogs of FMRP, the fragile X related protein 1 and 2.

Format

PDF

Language

English

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