PMID- 19388141
OWN - NLM
STAT- MEDLINE
DCOM- 20090518
LR  - 20211020
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 662
IP  - 1-2
DP  - 2009 Mar 9
TI  - Characterization of a novel splicing variant in the RAPTOR gene.
PG  - 88-92
AB  - The mammalian target of rapamycin (mTOR) plays an essential role in the 
      regulation of cell growth, proliferation and apoptosis. Raptor, the regulatory 
      associated protein of mTOR, is an important member in this signaling pathway. In 
      the present report,we identified and characterized a novel splicing variant of 
      this gene, RAPTOR v2, in which exons 14-17, 474 bp in total, are omitted from the 
      mRNA. This deletion does not change the open reading frame, but causes a nearly 
      complete absence of HEAT repeats, which were shown to be involved in the binding 
      of mTOR substrates. Real time PCR performed on 48 different human tissues 
      demonstrated the ubiquitous presence of this splice variant. Quantification of 
      mRNA levels in lymphoblastoid cell lines (LCL) from 56 unrelated HapMap 
      individuals revealed that the expression of this splicing form is quite variable. 
      One synonymous SNP, rs2289759 in exon 14, was predicted by ESEfinder to cause a 
      significant gain/loss of SRp55 and/or SF2/ASF binding sites, and thus potentially 
      influence splicing. This prediction was confirmed by linear regression analysis 
      between the ratio of RAPTOR v2 to total RAPTOR mRNA levels and the SNP genotype 
      in the above 56 individuals (r=0.281 and P=0.036). Moreover, the functional 
      evaluation indicated that this splicing isoform is expected to retain the ability 
      to bind mTOR, but is unlikely to bind mTOR substrates, hence affecting signal 
      transduction and further cell proliferation.
FAU - Sun, Chang
AU  - Sun C
AD  - Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. 
      csun1@bsd.uchicago.edu
FAU - Southard, Catherine
AU  - Southard C
FAU - Di Rienzo, Anna
AU  - Di Rienzo A
LA  - eng
GR  - U01 GM061393/GM/NIGMS NIH HHS/United States
GR  - U01GM61393/GM/NIGMS NIH HHS/United States
GR  - R01 DK056670/DK/NIDDK NIH HHS/United States
GR  - U01 GM061393-090006/GM/NIGMS NIH HHS/United States
GR  - R01 DK056670-08/DK/NIDDK NIH HHS/United States
GR  - R01DK056670/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RPTOR protein, human)
RN  - 0 (Regulatory-Associated Protein of mTOR)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Alternative Splicing/*genetics
MH  - Base Sequence
MH  - Cell Line
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Genotype
MH  - Humans
MH  - Molecular Sequence Data
MH  - Proteins/*genetics
MH  - RNA, Messenger/genetics/metabolism
MH  - Regulatory-Associated Protein of mTOR
PMC - PMC2724650
MID - NIHMS104530
COIS- Conflict of interest The authors declare that there are no conflicts of interest.
EDAT- 2009/04/24 09:00
MHDA- 2009/05/19 09:00
PMCR- 2009/08/11
CRDT- 2009/04/24 09:00
PHST- 2009/04/24 09:00 [entrez]
PHST- 2009/04/24 09:00 [pubmed]
PHST- 2009/05/19 09:00 [medline]
PHST- 2009/08/11 00:00 [pmc-release]
AID - S0027-5107(09)00016-5 [pii]
AID - 10.1016/j.mrfmmm.2009.01.001 [doi]
PST - ppublish
SO  - Mutat Res. 2009 Mar 9;662(1-2):88-92. doi: 10.1016/j.mrfmmm.2009.01.001.