RESUMO
BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive disorder caused by mutations in SMARCAL1. A frequent complication is arteriosclerosis associated with reduced elastin expression; however, the mechanism underlying the reduced elastin expression remains unknown. METHODS: Expression of transcriptional regulators of elastin (ELN) and microRNA (miRNA) regulators of ELN messenger RNA (mRNA), ELN promoter methylation, and ELN mRNA poly(A) tail length were assessed by quantitative RT-PCR, bisulfite Sanger sequencing, and the Poly(A) Tail Length Assay Kit, respectively, in unaffected developing human aortae and in an SIOD aorta. RESULTS: Comparing unaffected fetal and adult aortae, ELN precursor mRNA (pre-mRNA) levels remained nearly constant, whereas mRNA levels declined by ~10(2)-fold. This corresponded with a reduction in poly(A) tail length but not with changes in the other parameters. In contrast, compared to the unaffected fetal aortae, the SIOD aorta had 18-fold less ELN pre-mRNA and 10(4)-fold less mRNA. This corresponded with increased expression of miRNA regulators and shorter ELN mRNA poly(A) tail lengths but not with altered expression of ELN transcriptional regulators or ELN promoter methylation. CONCLUSION: Posttranscriptional mechanisms account for the reduction in ELN mRNA levels in unaffected aortae, whereas transcriptional and posttranscriptional mechanisms reduce elastin expression in SIOD aorta and predispose to arteriosclerosis.
Assuntos
Aorta/metabolismo , Arteriosclerose/genética , Elastina/genética , Síndromes de Imunodeficiência/genética , Síndrome Nefrótica/genética , Osteocondrodisplasias/genética , Embolia Pulmonar/genética , Precursores de RNA/genética , Processamento Pós-Transcricional do RNA , RNA Mensageiro/genética , Transcrição Gênica , Adolescente , Adulto , Aorta/embriologia , Aorta/patologia , Arteriosclerose/embriologia , Arteriosclerose/metabolismo , Arteriosclerose/patologia , Estudos de Casos e Controles , Células Cultivadas , Criança , Pré-Escolar , Metilação de DNA , Regulação para Baixo , Elastina/metabolismo , Feminino , Idade Gestacional , Humanos , Síndromes de Imunodeficiência/embriologia , Síndromes de Imunodeficiência/metabolismo , Síndromes de Imunodeficiência/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Síndrome Nefrótica/embriologia , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/patologia , Osteocondrodisplasias/embriologia , Osteocondrodisplasias/metabolismo , Osteocondrodisplasias/patologia , Doenças da Imunodeficiência Primária , Regiões Promotoras Genéticas , Embolia Pulmonar/embriologia , Embolia Pulmonar/metabolismo , Embolia Pulmonar/patologia , Precursores de RNA/metabolismo , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Global warming is causing rapid changes to the cryosphere. Predicting the future trajectory of the cryosphere requires quantitative reconstruction of its past variations. A recently identified sea-ice-associated haptophyte, known as Group 2i Isochrysidales, has given rise to a new sea-ice proxy with its characteristic alkenone distributions. However, apart from the occurrence of Group 2i Isochrysidales in regions with sea ice, and the empirical relationship between C37:4 alkenone abundance and sea-ice concentration, little is known about the ecology of these haptophyte species. Here, we systematically mapped the spatial and temporal occurrence of known Group 2i Isochrysidales based on environmental DNA in both marine and lacustrine environments. Our results indicate Group 2i is widely distributed in icy marine and lacustrine environments in both Northern and Southern Hemisphere, but is absent in warm environments. Temporally, Group 2i is part of the sea-ice algae bloom during the cold seasons, in contrast to other Isochrysidales that bloom in open waters during warm seasons. Our results indicate that ice is a prerequisite for the occurrence of the psychrophilic Group 2i haptophytes in marine and lacustrine ecosystems and further affirms its value for past ice reconstructions.