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Fragile X mental retardation protein recognizes a G quadruplex structure within the survival motor neuron domain containing 1 mRNA 5'-UTR.
- Source :
-
Molecular bioSystems [Mol Biosyst] 2017 Jul 25; Vol. 13 (8), pp. 1448-1457. - Publication Year :
- 2017
-
Abstract
- G quadruplex structures have been predicted by bioinformatics to form in the 5'- and 3'-untranslated regions (UTRs) of several thousand mature mRNAs and are believed to play a role in translation regulation. Elucidation of these roles has primarily been focused on the 3'-UTR, with limited focus on characterizing the G quadruplex structures and functions in the 5'-UTR. Investigation of the affinity and specificity of RNA binding proteins for 5'-UTR G quadruplexes and the resulting regulatory effects have also been limited. Among the mRNAs predicted to form a G quadruplex structure within the 5'-UTR is the survival motor neuron domain containing 1 (SMNDC1) mRNA, encoding a protein that is critical to the spliceosome. Additionally, this mRNA has been identified as a potential target of the fragile X mental retardation protein (FMRP), whose loss of expression leads to fragile X syndrome. FMRP is an RNA binding protein involved in translation regulation that has been shown to bind mRNA targets that form G quadruplex structures. In this study we have used biophysical methods to investigate G quadruplex formation in the 5'-UTR of SMNDC1 mRNA and analyzed its interactions with FMRP. Our results show that SMNDC1 mRNA 5'-UTR forms an intramolecular, parallel G quadruplex structure comprised of three G quartet planes, which is bound specifically by FMRP both in vitro and in mouse brain lysates. These findings suggest a model by which FMRP might regulate the translation of a subset of its mRNA targets by recognizing the G quadruplex structure present in their 5'-UTR, and affecting their accessibility by the protein synthesis machinery.
- Subjects :
- Amino Acid Sequence
Animals
Base Sequence
Binding Sites
Brain metabolism
Brain pathology
Fragile X Mental Retardation Protein genetics
Fragile X Mental Retardation Protein metabolism
Fragile X Syndrome genetics
Fragile X Syndrome metabolism
Fragile X Syndrome pathology
Gene Expression
Gene Expression Regulation
Humans
Mice
Protein Binding
Protein Biosynthesis
Protein Interaction Domains and Motifs
RNA Splicing Factors genetics
RNA Splicing Factors metabolism
Recombinant Proteins chemistry
Recombinant Proteins genetics
Recombinant Proteins metabolism
SMN Complex Proteins genetics
SMN Complex Proteins metabolism
Spliceosomes genetics
Spliceosomes metabolism
Thermodynamics
Transcription, Genetic
5' Untranslated Regions
Brain Chemistry
Fragile X Mental Retardation Protein chemistry
G-Quadruplexes
RNA Splicing Factors chemistry
SMN Complex Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1742-2051
- Volume :
- 13
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Molecular bioSystems
- Publication Type :
- Academic Journal
- Accession number :
- 28612854
- Full Text :
- https://doi.org/10.1039/c7mb00070g