RESUMO
Heterochromatin has essential functions in maintaining chromosome structure, in protecting genome integrity and in stabilizing gene expression programs. Heterochromatin is often nucleated by underlying DNA repeat sequences, such as major satellite repeats (MSR) and long interspersed nuclear elements (LINE). In order to establish heterochromatin, MSR and LINE elements need to be transcriptionally competent and generate non-coding repeat RNA that remain chromatin associated. We explored whether these heterochromatic RNA, similar to DNA and histones, may be methylated, particularly for 5-methylcytosine (5mC) or methyl-6-adenosine (m6A). Our analysis in mouse ES cells identifies only background level of 5mC but significant enrichment for m6A on heterochromatic RNA. Moreover, MSR transcripts are a novel target for m6A RNA modification, and their m6A RNA enrichment is decreased in ES cells that are mutant for Mettl3 or Mettl14, which encode components of a central RNA methyltransferase complex. Importantly, MSR transcripts that are partially deficient in m6A RNA methylation display impaired chromatin association and have a reduced potential to form RNA:DNA hybrids. We propose that m6A modification of MSR RNA will enhance the functions of MSR repeat transcripts to stabilize mouse heterochromatin.
Assuntos
DNA/metabolismo , Heterocromatina , RNA/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Metilação , Camundongos , Células-Tronco Embrionárias Murinas , Sequências de Repetição em TandemRESUMO
BACKGROUND/AIM: To be aware of the influencing factors of healthy aging, several cross-sectional surveys have been carried out among the elderly living in Austria to identify health and lifestyle factors as well as socioeconomic influences that contribute to the nutritional situation. METHODS: Information about the health situation was collected by questionnaires. Diet was assessed by both qualitative food frequency questionnaires and 24-hour recalls. Additionally, nutritional status was examined in blood and urine samples using static and functional parameters. RESULTS: The prevalence of overweight (21%, BMI >29) and obesity increased with increasing age up to 65 years; in people older than 65 years an inverse tendency could be observed; as from this age upwards a high prevalence of underweight was found (22%, BMI <24). The consumption of meat and meat products was too high compared to the recommendations. By contrast, the intake of high nutrient density foods was insufficient. On average, the fat intake was around 38% of total energy (%E); that of saturated fatty acids amounted to 20%E; the intake of carbohydrate and fiber was considered as being too low. The intake of folate, vitamin D, calcium, iodine, magnesium and vitamin C was assessed as inadequate. CONCLUSION: More attention has to be paid to certain micronutrients in order to optimize dietary intake and to sustain health.