Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: A role for Smn in RNA processing in motor axons?

Wilfried Rossol, Ann Kathrin Kröning, Uta Maria Ohndorf, Clemens Steegborn, Sibylle Jablonka, Michael Sendtner

Research output: Contribution to journalArticle

225 Citations (Scopus)

Abstract

Spinal muscular atrophy (SMA), the most common hereditary motor neuron disease in children and young adults is caused by mutations in the telomeric survival motor neuron (SMN1) gene. The human genome, in contrast to mouse, contains a second SMN gene (SMN2) which codes for a gene product which is alternatively spliced at the C-terminus, but also gives rise to low levels of full-length SMN protein. The reason why reduced levels of the ubiquitously expressed SMN protein lead to specific motor neuron degeneration without affecting other cell types is still not understood. Using yeast two-hybrid techniques, we identified hnRNP-R and the highly related gry-rbp/hnRNP-Q as novel SMN interaction partners. These proteins have previously been identified in the context of RNA processing, in particular mRNA editing, transport and splicing. hnRNP-R and gry-rbp/hnRNP-Q interact with wild-type Smn but not with truncated or mutant Smn forms identified in SMA. Both proteins are widely expressed and developmentally regulated with expression peaking at E19 in mouse spinal cord. hnRNP-R binds RNA through its RNA recognition motif domains. Interestingly, hnRNP-R is predominantly located in axons of motor neurons and co-localizes with Smn in this cellular compartment. Thus, this finding could provide a key to understand a motor neuron-specific Smn function in SMA.

Original languageEnglish (US)
Pages (from-to)93-105
Number of pages13
JournalHuman Molecular Genetics
Volume11
Issue number1
StatePublished - Jan 1 2002
Externally publishedYes

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Heterogeneous-Nuclear Ribonucleoproteins
Spinal Muscular Atrophy
Axons
Motor Neurons
RNA
Genes
Proteins
Nerve Degeneration
Motor Neuron Disease
Human Genome
Young Adult
Spinal Cord
Yeasts
Messenger RNA
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q : A role for Smn in RNA processing in motor axons? / Rossol, Wilfried; Kröning, Ann Kathrin; Ohndorf, Uta Maria; Steegborn, Clemens; Jablonka, Sibylle; Sendtner, Michael.

In: Human Molecular Genetics, Vol. 11, No. 1, 01.01.2002, p. 93-105.

Research output: Contribution to journalArticle

Rossol, Wilfried ; Kröning, Ann Kathrin ; Ohndorf, Uta Maria ; Steegborn, Clemens ; Jablonka, Sibylle ; Sendtner, Michael. / Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q : A role for Smn in RNA processing in motor axons?. In: Human Molecular Genetics. 2002 ; Vol. 11, No. 1. pp. 93-105.
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