期刊
MOLECULAR BIOSYSTEMS
卷 13, 期 8, 页码 1448-1457出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7mb00070g
关键词
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资金
- President's Mentorship Fund
- College Research Council grants of University of Pittsburgh at Johnstown
- NIH [9R15HD078017-03A1, 1R21NS089080]
- NSF REU
- MRI [CHE-1263279, CHE-1126465]
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.
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