Contemporary retrotransposition of a novel non-coding gene induces exon-skipping in dystrophin mRNA.
Summary of "Contemporary retrotransposition of a novel non-coding gene induces exon-skipping in dystrophin mRNA."
Non-autonomous retrotransposon-mediated mobilizations of the Alu family are known pathogenic mechanisms of human disease. Here, we report a pathogenic, contemporary, non-autonomous retrotransmobilization of part of a novel non-coding gene into the dystrophin gene. In a Japanese Duchenne muscular dystrophy patient, a 330-bp-long de novo insertion was identified in exon 67 of dystrophin. The insertion induced exon 67-skipping in the dystrophin mRNA, creating a premature stop codon. The sequence of the insertion had certain characteristics of retrotransposons: an antisense polyadenylation signal accompanied by a poly(T) sequence and a target site duplication. The insertion site matched the consensus recognition sequence for the L1 endonuclease, indicating a retrotransposon-mediated event, although the inserted sequence did not match any known retrotransposons. The origin of the inserted sequence was mapped to a gene-poor region of chromosome 11. The inserted fragment was expressed in multiple human tissue RNAs, indicating that it is a novel transcript. The full length of the transcript was cloned and showed no meaningful protein coding ability.Journal of Human Genetics advance online publication, 9 September 2010; doi:10.1038/jhg.2010.111.
Affiliation
Department of Pediatrics, Graduate School of Medicine, Kobe University, Kobe, Japan.
Journal Details
This article was published in the following journal.
Name: Journal of human genetics
ISSN: 1435-232X
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20827276
- DOI: http://dx.doi.org/10.1038/jhg.2010.111
Medical and Biotech [MESH] Definitions
Gene Rearrangement, T-lymphocyte
Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.
Gene Rearrangement, B-lymphocyte
Ordered rearrangement of B-lymphocyte variable gene regions coding for the IMMUNOGLOBULIN CHAINS, thereby contributing to antibody diversity. It occurs during the differentiation of the IMMATURE B-LYMPHOCYTES.
Alternative Splicing
A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.
Polypyrimidine Tract-binding Protein
A RNA-binding protein that binds to polypyriminidine rich regions in the INTRONS of messenger RNAs. Polypyrimidine tract-binding protein may be involved in regulating the ALTERNATIVE SPLICING of mRNAs since its presence on an intronic RNA region that is upstream of an EXON inhibits the splicing of the exon into the final mRNA product.
Gene Rearrangement, B-lymphocyte, Light Chain
Ordered rearrangement of B-lymphocyte variable gene regions coding for the kappa or lambda IMMUNOGLOBULIN LIGHT CHAINS, thereby contributing to antibody diversity. It occurs during the second stage of differentiation of the IMMATURE B-LYMPHOCYTES.
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