Journal Article

IGHMBP2 is a ribosome-associated helicase inactive in the neuromuscular disorder distal SMA type 1 (DSMA1)

Ulf-Peter Guenther, Lusy Handoko, Bernhard Laggerbauer, Sibylle Jablonka, Ashwin Chari, Mona Alzheimer, Jürgen Ohmer, Oliver Plöttner, Niels Gehring, Albert Sickmann, Katja von Au, Markus Schuelke and Utz Fischer

in Human Molecular Genetics

Volume 18, issue 7, pages 1288-1300
Published in print April 2009 | ISSN: 0964-6906
Published online January 2009 | e-ISSN: 1460-2083 | DOI:
IGHMBP2 is a ribosome-associated helicase inactive in the neuromuscular disorder distal SMA type 1 (DSMA1)

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Distal spinal muscular atrophy type 1 (DSMA1) is an autosomal recessive disease that is clinically characterized by distal limb weakness and respiratory distress. In this disease, the degeneration of α-motoneurons is caused by mutations in the immunoglobulin μ-binding protein 2 (IGHMBP2). This protein has been implicated in DNA replication, pre-mRNA splicing and transcription, but its precise function in all these processes has remained elusive. We have purified catalytically active recombinant IGHMBP2, which has enabled us to assess its enzymatic properties and to identify its cellular targets. Our data reveal that IGHMBP2 is an ATP-dependent 5′→3′ helicase, which unwinds RNA and DNA duplices in vitro. Importantly, this helicase localizes predominantly to the cytoplasm of neuronal and non-neuronal cells and associates with ribosomes. DSMA1-causing amino acid substitutions in IGHMBP2 do not affect ribosome binding yet severely impair ATPase and helicase activity. We propose that IGHMBP2 is functionally linked to translation, and that mutations in its helicase domain interfere with this function in DSMA1 patients.

Journal Article.  8531 words.  Illustrated.

Subjects: Genetics and Genomics

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