Fragile X mental retardation protein interactions with the microtubule associated protein 1B RNA.
Fragile X mental retardation syndrome, the most common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP). FMRP has been shown to use its arginine-glycine-glycine (RGG) box to bind to a subset of RNA targets that form a G quadruplex structure. We performed a detailed analysis of the interactions between the FMRP RGG box and the microtubule associated protein 1B (MAP1B) mRNA, a relevant in vivo FMRP target. We show that MAP1B RNA forms an intramolecular G quadruplex structure, which is bound with high affinity and specificity by the FMRP RGG box. We determined that hydrophobic interactions are important in the FMRP RGG box-MAP1B RNA association, with minor contributions from electrostatic interactions. Our findings that at low protein:RNA ratios the RNA G quadruplex structure is slightly stabilized, whereas at high ratios is unfolded, suggest a mechanism by which the FMRP concentration variation in response to a neurotransmitter stimulation event could act as a regulatory switch for the protein function, from translation repressor to translation activator.
Menon
Lakshmi
L
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania 15282, USA.
Mader
Samantha Ann
SA
Mihailescu
Mihaela-Rita
MR
D000818:Animals; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
D051860:Fragile X Messenger Ribonucleoprotein 1; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; C085284:microtubule-associated protein 1B