PMID- 9563950
OWN - NLM
STAT- MEDLINE
DCOM- 19980518
LR  - 20240104
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 280
IP  - 5364
DP  - 1998 May 1
TI  - Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy.
PG  - 737-41
AB  - Myotonic dystrophy (DM) is caused by a CTG expansion in the 3' untranslated 
      region of the DM gene. One model of DM pathogenesis suggests that RNAs from the 
      expanded allele create a gain-of-function mutation by the inappropriate binding 
      of proteins to the CUG repeats. Data presented here indicate that the conserved 
      heterogeneous nuclear ribonucleoprotein, CUG-binding protein (CUG-BP), may 
      mediate the trans-dominant effect of the RNA. CUG-BP was found to bind to the 
      human cardiac troponin T (cTNT) pre-messenger RNA and regulate its alternative 
      splicing. Splicing of cTNT was disrupted in DM striated muscle and in normal 
      cells expressing transcripts that contain CUG repeats. Altered expression of 
      genes regulated posttranscriptionally by CUG-BP therefore may contribute to DM 
      pathogenesis.
FAU - Philips, A V
AU  - Philips AV
AD  - Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
FAU - Timchenko, L T
AU  - Timchenko LT
FAU - Cooper, T A
AU  - Cooper TA
LA  - eng
GR  - AR 44387/AR/NIAMS NIH HHS/United States
GR  - HL45565/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (CELF1 Protein)
RN  - 0 (CELF1 protein, human)
RN  - 0 (DMPK protein, human)
RN  - 0 (RNA Precursors)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Ribonucleoproteins)
RN  - 0 (Troponin)
RN  - 0 (Troponin T)
RN  - EC 2.7.11.1 (Myotonin-Protein Kinase)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
CIN - Science. 1998 May 1;280(5364):696-7. PMID: 9599147
MH  - *Alternative Splicing
MH  - CELF1 Protein
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Exons
MH  - Humans
MH  - Introns
MH  - Muscle, Skeletal/cytology/embryology/metabolism
MH  - Mutation
MH  - Myotonic Dystrophy/*genetics/metabolism
MH  - Myotonin-Protein Kinase
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*genetics
MH  - RNA Precursors/metabolism
MH  - RNA, Messenger/*genetics/metabolism
MH  - RNA-Binding Proteins/genetics/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Ribonucleoproteins/genetics/*metabolism
MH  - Transcription, Genetic
MH  - Transfection
MH  - *Trinucleotide Repeats
MH  - Troponin/genetics
MH  - Troponin T
EDAT- 1998/05/23 00:00
MHDA- 1998/05/23 00:01
CRDT- 1998/05/23 00:00
PHST- 1998/05/23 00:00 [pubmed]
PHST- 1998/05/23 00:01 [medline]
PHST- 1998/05/23 00:00 [entrez]
AID - 10.1126/science.280.5364.737 [doi]
PST - ppublish
SO  - Science. 1998 May 1;280(5364):737-41. doi: 10.1126/science.280.5364.737.