RGD Reference Report - LDB3 splicing abnormalities are specific to skeletal muscles of patients with myotonic dystrophy type 1 and alter its PKC binding affinity. - Rat Genome Database

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LDB3 splicing abnormalities are specific to skeletal muscles of patients with myotonic dystrophy type 1 and alter its PKC binding affinity.

Authors: Yamashita, Yoshihiro  Matsuura, Tohru  Kurosaki, Tatsuaki  Amakusa, Yoshinobu  Kinoshita, Masanobu  Ibi, Tohru  Sahashi, Ko  Ohno, Kinji 
Citation: Yamashita Y, etal., Neurobiol Dis. 2014 Sep;69:200-5. doi: 10.1016/j.nbd.2014.05.026. Epub 2014 May 27.
RGD ID: 12792205
Pubmed: PMID:24878509   (View Abstract at PubMed)
DOI: DOI:10.1016/j.nbd.2014.05.026   (Journal Full-text)

Myotonic dystrophy type 1 (DM1) is caused by transcription of CUG repeat RNA, which causes sequestration of muscleblind-like 1 (MBNL1) and upregulation of CUG triplet repeat RNA-binding protein (CUG-BP1). In DM1, dysregulation of these proteins contributes to many aberrant splicing events, causing various symptoms of the disorder. Here, we demonstrate the occurrence of aberrant splicing of LIM domain binding 3 (LDB3) exon 11 in DM1 skeletal muscle. Exon array surveys, RT-PCR, and western blotting studies demonstrated that exon 11 inclusion was DM1 specific and could be reproduced by transfection of a minigene containing the CTG repeat expansion. Moreover, we found that the LDB3 exon 11-positive isoform had reduced affinity for PKC compared to the exon 11-negative isoform. Since PKC exhibits hyperactivation in DM1 and stabilizes CUG-BP1 by phosphorylation, aberrant splicing of LDB3 may contribute to CUG-BP1 upregulation through changes in its affinity for PKC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
myotonic dystrophy type 1  IEP 12792205mRNA and protein:alternative form:exonRGD 
myotonic dystrophy type 1  ISOLDB3 (Homo sapiens)12792205; 12792205mRNA and protein:alternative form:exonRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ldb3  (LIM domain binding 3)

Genes (Mus musculus)
Ldb3  (LIM domain binding 3)

Genes (Homo sapiens)
LDB3  (LIM domain binding 3)


Additional Information