The mouse synemin gene encodes three intermediate filament proteins generated by alternative exon usage and different open reading frames.
We have previously cloned and characterized the human synemin gene, which encodes two intermediate filament proteins (IFPs). We now show that the mouse synemin gene encodes three different synemin isoforms through an alternative splicing mechanism. Two of them, synemin H and M are similar to human alpha and beta synemin, and the third isoform, L synemin, constitutes a new form of IFP. It has a typical rod domain and a short tail (49 residues) with a novel sequence that is produced by a different open reading frame. The synthesis of H/M synemins starts in the embryo, whereas the synemin L isoform is present in adult muscles. The H/M isoforms are bound to desmin or vimentin in the muscle cells of wild-type mice. Using desmin- and vimentin-deficient mice, we have obtained direct evidence that synemin is associated with muscle intermediate filaments in vivo. The organization of the synemin fibril is disrupted in skeletal and cardiac muscle when desmin is absent and in smooth muscle when vimentin is absent. The fact that the three synemin isoforms differ in the sequences of their tail domains as well as in their developmental patterns suggests that they fulfill different functions.
Xue
Z G
ZG
Biologie Moléculaire de la Différenciation, Department of Biochemistry, Université Denis Diderot Paris7, 75005 Paris, France. xue@ccr.jussieu.fr
Cheraud
Y
Y
Brocheriou
V
V
Izmiryan
A
A
Titeux
M
M
Paulin
D
D
Li
Z
Z
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D003893:Desmin / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005333:Fetus; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D016366:Open Reading Frames / Q000235:genetics; D009928:Organ Specificity; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D018076:DNA, Complementary; D003893:Desmin; D007381:Intermediate Filament Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D014746:Vimentin; C430456:desmuslin; C491443:synemin protein, mouse