A role for the RNA-binding protein, hermes, in the regulation of heart development.
RNA-binding proteins are known to play an important role in a number of aspects of development, although in most cases the precise mechanism of action remains unknown. We have previously described the isolation of an RNA-binding protein, hermes, that is expressed at very high levels in the differentiating myocardium. Here, we report experiments aimed at elucidating the functional role of hermes in development. Utilizing the Xenopus oocyte, we show that hermes is localized primarily to the cytoplasm, can associate in a multiprotein complex, and is able to bind to mature RNA transcripts in vivo. Overexpression of hermes in the developing embryo dramatically and specifically inhibits heart development. In particular, transcripts encoding the myocardial differentiation markers, cardiac troponin I and cardiac alpha-actin, are absent, and overall morphological development of the heart is eliminated. Examination of markers of precardiac tissue showed that expression of GATA-4 is normal, while the levels of Nkx2-5 mRNA are strongly reduced. Overall, these studies suggest that hermes plays a role in the regulation of mature transcripts required for myocardial differentiation. To our knowledge, this is the first evidence for an RNA-binding protein playing a direct role in regulation of vertebrate heart development.
Gerber
Wendy V
WV
Department of Cell Biology and Anatomy, University of Arizona Health Sciences Center, Tucson 85724, USA.
Vokes
Steven A
SA
Zearfoss
N Ruth
NR
Krieg
Paul A
PA
D000199:Actins / Q000502:physiology; D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000502:physiology; D050991:GATA4 Transcription Factor; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000502:physiology; D009024:Morphogenesis; D009124:Muscle Proteins / Q000502:physiology; D016601:RNA-Binding Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D019210:Troponin I / Q000502:physiology; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology / Q000502:physiology
D000199:Actins; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; C494751:GATA4 protein, Xenopus; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D009124:Muscle Proteins; C092720:NKX2-5 protein, Xenopus; C095552:NKX2-5 protein, human; C484469:Nkx2-5 protein, mouse; C485602:RBPMS2 protein, Xenopus; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D019210:Troponin I; D029867:Xenopus Proteins