Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons.
Spinal muscular atrophy (SMA), a common autosomal recessive form of motoneuron disease in infants and young adults, is caused by mutations in the survival motoneuron 1 (SMN1) gene. The corresponding gene product is part of a multiprotein complex involved in the assembly of spliceosomal small nuclear ribonucleoprotein complexes. It is still not understood why reduced levels of the ubiquitously expressed SMN protein specifically cause motoneuron degeneration. Here, we show that motoneurons isolated from an SMA mouse model exhibit normal survival, but reduced axon growth. Overexpression of Smn or its binding partner, heterogeneous nuclear ribonucleoprotein (hnRNP) R, promotes neurite growth in differentiating PC12 cells. Reduced axon growth in Smn-deficient motoneurons correlates with reduced beta-actin protein and mRNA staining in distal axons and growth cones. We also show that hnRNP R associates with the 3' UTR of beta-actin mRNA. Together, these data suggest that a complex of Smn with its binding partner hnRNP R interacts with beta-actin mRNA and translocates to axons and growth cones of motoneurons.
Rossoll
Wilfried
W
Institute for Clinical Neurobiology, University of Wuerzburg, 97080 Wuerzburg, Germany.
Jablonka
Sibylle
S
Andreassi
Catia
C
Kröning
Ann-Kathrin
AK
Karle
Kathrin
K
Monani
Umrao R
UR
Sendtner
Michael
M
D020413:3' Untranslated Regions / Q000235:genetics; D000199:Actins / Q000235:genetics*; D000818:Animals; D001369:Axons / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein; D004195:Disease Models, Animal; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D051381:Rats; D055532:SMN Complex Proteins; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D055533:Survival of Motor Neuron 1 Protein
D020413:3' Untranslated Regions; D000199:Actins; D017362:Cyclic AMP Response Element-Binding Protein; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526472:Smn1 protein, mouse; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein