PMID- 21237174
OWN - NLM
STAT- MEDLINE
DCOM- 20110418
LR  - 20211020
IS  - 1089-8638 (Electronic)
IS  - 0022-2836 (Print)
IS  - 0022-2836 (Linking)
VI  - 407
IP  - 1
DP  - 2011 Mar 18
TI  - Initiation of translation of the FMR1 mRNA Occurs predominantly through 
      5'-end-dependent ribosomal scanning.
PG  - 21-34
LID - 10.1016/j.jmb.2011.01.006 [doi]
AB  - The fragile X mental retardation 1 (FMR1) gene contains a CGG repeat within its 
      5' untranslated region (5'UTR) that, when expanded to 55-200 CGG repeats 
      (premutation allele), can result in the late-onset neurodegenerative disorder, 
      fragile X-associated tremor/ataxia syndrome. The CGG repeat is expected to form a 
      highly stable secondary structure that is capable of inhibiting 5'-cap-dependent 
      translation. Paradoxically, translation in vivo is only mildly impaired within 
      the premutation range, suggesting that other modes of translation initiation may 
      be operating. To address this issue, we translated in vitro a set of reporter 
      mRNAs containing between 0 and 99 CGG repeats in either native (FMR1) or 
      unrelated (heterologous) 5'UTR context. The 5'-cap dependence of translation was 
      assessed by inserting a stable hairpin (HP) near the 5' end of the mRNAs. The 
      results of the current studies indicate that translation initiation of the FMR1 
      mRNA occurs primarily by scanning, with little evidence of internal ribosome 
      entry or shunting. Additionally, the efficiency of translation initiation depends 
      on transcription start site selection, with the shorter 5'UTR (downstream 
      transcription start site I) translating with greater efficiency compared to the 
      longer mRNA (start site III) for all CGG-repeat elements studied. Lastly, an HP 
      previously shown to block translation gave differing results depending on the 
      5'UTR context, in one case initiating translation from within the HP.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Ludwig, Anna L
AU  - Ludwig AL
AD  - Department of Biochemistry and Molecular Medicine, University of California Davis 
      School of Medicine, Davis, CA 95616, USA.
FAU - Hershey, John W B
AU  - Hershey JW
FAU - Hagerman, Paul J
AU  - Hagerman PJ
LA  - eng
GR  - R01 HD040661-09/HD/NICHD NIH HHS/United States
GR  - UL1 DE019583-04/DE/NIDCR NIH HHS/United States
GR  - UL1 DE019583/DE/NIDCR NIH HHS/United States
GR  - RL1AG032119/AG/NIA NIH HHS/United States
GR  - RL1 AG032119-04/AG/NIA NIH HHS/United States
GR  - R01 HD040661/HD/NICHD NIH HHS/United States
GR  - RL1 AG032119/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110112
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (5' Untranslated Regions)
RN  - 0 (RNA, Messenger)
RN  - 139135-51-6 (Fragile X Mental Retardation Protein)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - 5' Untranslated Regions/*genetics
MH  - Fragile X Mental Retardation Protein/*genetics/metabolism
MH  - Humans
MH  - Luciferases/genetics/metabolism
MH  - *Protein Biosynthesis
MH  - RNA, Messenger/chemistry/*genetics/metabolism
MH  - Ribosomes/*physiology
MH  - *Transcription Initiation Site
MH  - Transcription, Genetic
MH  - Trinucleotide Repeat Expansion
PMC - PMC3046292
MID - NIHMS265968
EDAT- 2011/01/18 06:00
MHDA- 2011/04/19 06:00
PMCR- 2012/03/18
CRDT- 2011/01/18 06:00
PHST- 2010/11/25 00:00 [received]
PHST- 2011/01/04 00:00 [revised]
PHST- 2011/01/04 00:00 [accepted]
PHST- 2011/01/18 06:00 [entrez]
PHST- 2011/01/18 06:00 [pubmed]
PHST- 2011/04/19 06:00 [medline]
PHST- 2012/03/18 00:00 [pmc-release]
AID - S0022-2836(11)00023-4 [pii]
AID - 10.1016/j.jmb.2011.01.006 [doi]
PST - ppublish
SO  - J Mol Biol. 2011 Mar 18;407(1):21-34. doi: 10.1016/j.jmb.2011.01.006. Epub 2011 
      Jan 12.