Protein complex clears potential traffic jams in RNA production, finds research

Agencies
April 6, 2019

April 6: A new research has found that a protein complex plays a key role in clearing potential traffic jams in the production of RNA.

The research was published in the journal Genes & Development.

"The 'Ccr4-Not' complex is involved in nearly every step of this process from start to finish. Our new research shows that this complex has an additional function that helps maintain normal cellular function when something goes wrong during transcription," said Joseph C. Reese, a researcher.

During the transcription of RNA from DNA, RNAPII, itself a large complex made up of multiple protein subunits, travels along the strand of DNA reading the ATCG sequence and producing a complementary strand of RNA.

If the RNAPII encounters DNA damage, which can be caused by UV radiation and other sources, it can become stuck and prevent trailing polymerases from completing transcription of the gene, similar to how a stalled car prevents traffic behind it from flowing.

If this jam cannot be cleared, multiple RNAPIIs transcribing the same gene can start to pile up in a sort of traffic jam preventing the DNA from being repaired and hampering cell function.

"Defects in this pathway have been associated with a number of diseases and human syndromes, such as Cockayne syndrome- a neurodegenerative disorder that results in growth failure, neurological developmental defects, and sensitivity to UV light," Reese added.

RNA polymerase II (RNAPII), the enzyme that produces RNA from a DNA template, can become stuck due to damage to the DNA template, and these jams must be cleared to restore gene expression and normal cell function.

New research shows that the master regulatory complex, 'Ccr4-Not' performs this task, associating with RNAPII during the transcription of RNA from DNA and marking RNAPII for degradation when it becomes stuck, allowing the DNA to be repaired and normal cell function to resume.

"Normal cellular functions rely on what is sometimes called the 'central dogma of biology,'" said Reese.

The researchers used genetic methods and reconstitution biochemistry- a method whereby purified components of a cellular process can be added- taken away, and mixed in a precisely controlled manner to identify exactly how they function to show that 'Ccr4-Not' recruits factors that mark RNAPII with a small signalling molecule called ubiquitin.Attachment of ubiquitin to RNAPII triggers other cellular components to degrade the enzyme, clearing the jam.

"Mutating members of the 'Ccr4-Not' complex makes cells more sensitive to agents that damage the genome, but because 'Ccr4-Not' is involved in so many aspects of gene regulation it wasn't clear until now what its precise role was," said Reese.

"The fact that 'Ccr4-Not' recruited the destruction machinery to RNAPII was a surprising result, and suggests it acts as a tow truck to remove traffic jams throughout the genome," he added.

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Agencies
January 11,2020

Europe, Jan 11: Researchers have revealed the people who drink tea at least three times a week have healthy years of life and longer life expectancy.

The research was published in the European Journal of Preventive Cardiology, a journal of the European Society of Cardiology (ESC).

Dr Xinyan Wang, who is the author of the study, said: "Habitual tea consumption is associated with lower risks of cardiovascular disease and all-cause death. The favourable health effects are the most robust for green tea and for long-term habitual tea drinkers."
The analysis that was conducted included about 100,902 participants of the China-PAR project2 with no history of heart attack, stroke, or cancer.

Participants were classified into two groups: Habitual tea drinkers and never or non-habitual tea drinkers and followed-up for a median of 7.3 years.

The analyses estimated that 50-year-old habitual tea drinkers would develop coronary heart disease and stroke 1.41 years later and live 1.26 years longer than those who never or seldom drank tea. Compared with never or non-habitual tea drinkers, the habitual tea consumers had a 20 per cent lower risk of incident heart disease and stroke, 22 per cent lower risk of fatal heart disease and stroke, and 15 per cent decreased risk of all-cause death.

The potential influence of changes in tea drinking behaviour was suspected in a subset of 14,081 participants with assessments at two-time points. The average duration between the two surveys was 8.2 years, and the median follow-up after the second survey was 5.3 years.

Habitual tea drinkers who maintained their habit in both surveys had a 39 per cent lower risk of incident heart disease and stroke, 56 per cent lower risk of fatal heart disease and stroke, and 29 per cent decreased risk of all-cause death compared to consistent never or non-habitual tea drinkers.

Senior author Dr Dongfeng Gu said: "The protective effects of tea were most pronounced among the consistent habitual tea drinking group. Mechanism studies have suggested that the main bioactive compounds in tea, namely polyphenols, are not stored in the body long-term. Thus, frequent tea intake over an extended period may be necessary for the cardioprotective effect."

In a subanalysis by type of tea, drinking green tea was linked with approximately 25 per cent lower risks for incident heart disease and stroke, fatal heart disease and stroke, and all-cause death. However, no significant associations were observed for black tea.
Dr Gu noted that a preference for green tea is unique to East Asia.

Two factors may be at play. First, green tea is a rich source of polyphenols which protect against cardiovascular disease and its risk factors including high blood pressure and dyslipidaemia. Black tea is fully fermented and during this process, polyphenols are oxidised into pigments and may lose their antioxidant effects. Second, black tea is often served with milk, which previous research has shown may counteract the favourable health effects of tea on vascular function.

Gender-specific analyses showed that the protective effects of habitual tea consumption were pronounced and robust across different outcomes for men, but only modest for women. Dr Wang said: "One reason might be that 48 per cent of men were habitual tea consumers compared to just 20 per cent of women. Secondly, women had a much lower incidence of, and mortality from, heart disease and stroke. These differences made it more likely to find statistically significant results among men."

She said: "The China-PAR project is ongoing, and with more person-years of follow-up among women the associations may become more pronounced."

In conclusion, the authors have found that randomised trials are required to validate the results and to illustrate nutritional guidelines and advice for lifestyle.

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Agencies
February 27,2020

Washington D.C, Feb 27: New research shows that adults who have low fruit and vegetable intake are more likely to be diagnosed with an anxiety disorder.

"For those who consumed less than 3 sources of fruits and vegetables daily, there was at least at 24% higher odds of anxiety disorder diagnosis," says the lead author of the Canadian Longitudinal Study, Karen Davison, who is a health science faculty member, nutrition informatics lab director at Kwantlen Polytechnic University, (KPU) and North American Primary Care Research Group Fellow.

"This may also partly explain the findings associated with body composition measures. As levels of total body fat increased beyond 36%, the likelihood of anxiety disorder was increased by more than 70%," states co-author Jose Mora-Almanza, a Mitacs Globalink intern who worked with the study at KPU.

"Increased body fat may be linked to greater inflammation. Emerging research suggests that some anxiety disorders can be linked to inflammation," says Davison.

In addition to diet and body composition measures, the prevalence of anxiety disorders also differed by gender, marital status, income, immigrant status and several health issues.

An important limitation of the study was that the assessment of anxiety disorders was mostly based upon self-reporting of a medical diagnosis.

"It is estimated that 10% of the global population will suffer from anxiety disorders which are a leading cause of disability," says Karen Davison

"Our findings suggest that comprehensive approaches that target health behaviours, including diet, as well as social factors, such as economic status, may help to minimize the burden of anxiety disorders among middle-aged and older adults, including immigrants," she concluded.

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Agencies
April 17,2020

Washington DC, Apr 17: In recent research, scientists have linked the emotional, social and psychiatric problems in children and adolescents with higher levels of genetic vulnerability for adult depression. The study implies that the genetics passed from parents may be linked with psychiatric problems in children and adolescents and may also leading to depression in adults.

University of Queensland scientists made the finding while analysing the genetic data of more than 42,000 children and adolescents from seven cohorts across Finland, the Netherlands, Norway, Sweden and the UK.

Professor Christel Middeldorp said that researchers have also found a link with a higher genetic vulnerability for insomnia, neuroticism and body mass index.

"By contrast, study participants with higher genetic scores for educational attainment and emotional well-being were found to have reduced childhood problems," Professor Middeldorp said.

"We calculated a person's level of genetic vulnerability by adding up the number of risk genes they had for a specific disorder or trait and then made adjustments based on the level of importance of each gene We found the relationship was mostly similar across ages," Middeldorp added.

The results indicate there are shared genetic factors that affect a range of psychiatric and related traits across a person's lifespan.

Middeldorp said that around 50 per cent of children and adolescents with psychiatric problems, such as attention deficit hyperactivity disorder (ADHD), continue to experience mental disorders as adults, and are at risk of disengaging with their school community among other social and emotional problems.

"Our findings are important as they suggest this continuity between childhood and adult traits is partly explained by genetic risk," the Professor said.

"Individuals at risk of being affected should be the focus of attention and targeted treatment," Middeldorp continued.

"Although the genetic vulnerability is not accurate enough at this stage to make individual predictions about how a person's symptoms will develop over time, it may become so in the future, in combination with other risk factors. And, this may support precision medicine by providing targeted treatments to children at the highest risk of persistent emotional and social problems," Middeldorp added.

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