PMID- 18579868 OWN - NLM STAT- MEDLINE DCOM- 20080812 LR - 20211020 IS - 1469-9001 (Electronic) IS - 1355-8382 (Print) IS - 1355-8382 (Linking) VI - 14 IP - 8 DP - 2008 Aug TI - Fragile X mental retardation protein interactions with the microtubule associated protein 1B RNA. PG - 1644-55 LID - 10.1261/rna.1100708 [doi] AB - 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. FAU - Menon, Lakshmi AU - Menon L AD - Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania 15282, USA. FAU - Mader, Samantha Ann AU - Mader SA FAU - Mihailescu, Mihaela-Rita AU - Mihailescu MR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20080625 PL - United States TA - RNA JT - RNA (New York, N.Y.) JID - 9509184 RN - 0 (Microtubule-Associated Proteins) RN - 0 (RNA, Messenger) RN - 0 (microtubule-associated protein 1B) RN - 139135-51-6 (Fragile X Mental Retardation Protein) SB - IM MH - Animals MH - Fragile X Mental Retardation Protein/chemistry/*metabolism MH - Humans MH - Microtubule-Associated Proteins/*genetics/*metabolism MH - Protein Biosynthesis MH - Protein Structure, Tertiary MH - RNA, Messenger/chemistry/metabolism MH - Thermodynamics PMC - PMC2491469 EDAT- 2008/06/27 09:00 MHDA- 2008/08/13 09:00 PMCR- 2009/02/01 CRDT- 2008/06/27 09:00 PHST- 2008/06/27 09:00 [pubmed] PHST- 2008/08/13 09:00 [medline] PHST- 2008/06/27 09:00 [entrez] PHST- 2009/02/01 00:00 [pmc-release] AID - rna.1100708 [pii] AID - RA [pii] AID - 10.1261/rna.1100708 [doi] PST - ppublish SO - RNA. 2008 Aug;14(8):1644-55. doi: 10.1261/rna.1100708. Epub 2008 Jun 25.