Csm, a cardiac-specific isoform of the RNA helicase Mov10l1, is regulated by Nkx2.5 in embryonic heart.
Nkx2.5 (also called Csx) is an evolutionarily conserved cardiac transcription factor of the homeobox gene family. Nkx2.5 is required for early heart development, because Nkx2.5 null mice die before completion of cardiac looping. To identify genes regulated by Nkx2.5 in the developing heart, we performed differential screening in combination with suppression subtractive hybridization using RNA isolated from wild-type and Nkx2.5 null hearts at embryonic day 8.5. One gene that we found to be markedly down-regulated in the hearts from Nkx2.5 null embryos is an isoform of Mov10 like-1 (Mov10l1), a putative RNA helicase expressed in testis. We named this novel isoform as Csm (cardiac-specific isoform of Mov10l1). Csm is identical with the 3' region of the Mov10l1 gene, but its transcript starts from the exon 16 of Mov10l1. The conceptual protein encoded by Csm cDNA contains a helicase motif as well as ATPase and RNA interaction motifs. Csm is expressed specifically in the heart, and its expression in the heart is restricted to cardiac myocytes. Csm potentiated phenylephrine-induced hypertrophic response in cardiac myocytes. Furthermore, transient cotransfection analysis showed that Nkx2.5 transactivates the Csm promoter, suggesting that Nkx2.5 is essential for embryonic Csm expression.
Ueyama
Tomomi
T
Cardiovascular Division, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
Kasahara
Hideko
H
Ishiwata
Takahiro
T
Yamasaki
Naohito
N
Izumo
Seigo
S
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D016384:Consensus Sequence; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology*; D009693:Nucleic Acid Hybridization; D010656:Phenylephrine / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D020365:RNA Helicases / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000201:enzymology; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection; D029867:Xenopus Proteins
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D029867:Xenopus Proteins; D010656:Phenylephrine; C477006:Mov10l1 protein, mouse; D020365:RNA Helicases