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.

Comments

Add new comment

  • Coastaldigest.com reserves the right to delete or block any comments.
  • Coastaldigset.com is not responsible for its readers’ comments.
  • Comments that are abusive, incendiary or irrelevant are strictly prohibited.
  • Please use a genuine email ID and provide your name to avoid reject.
News Network
January 31,2020

Jan 31: Cervical cancer could be eliminated worldwide as a public health issue within the next 100 years, according to two studies which may lead to better strategies for screening and vaccination against the malignant disease.

According to the studies, published in the journal The Lancet, more than 74 million cervical cancer cases, and 60 million deaths could be averted, and the disease eliminated in the 78 countries which have the highest disease burden.

The researchers, including those from Laval University in Canada, said cervical cancer is the second most frequent cancer among women in low-income and lower-middle-income countries (LMICs) with 2,90,000 (51 per cent) of the 5,70,000 new cases worldwide reported in women living in LMICs.

In the current studies, the scientists used the WHO draft strategy of cervical cancer elimination which defines plans for vaccination against the disease's causative agent, the human papillomavirus (HPV).

These plans, they explained, call for 90 per cent of girls to be vaccinated against HPV by 2030, and for 70 per cent of women to be screened for cervical cancer once or twice in their lifetime.

About 90 per cent of women with precancerous lesions, or cervical cancer are also advised to receive appropriate treatment, according to the WHO draft strategy, the scientists said.

In the second study, the research team analysed the impact of three elements of the WHO strategy on deaths from cervical cancer -- modelling the impact of scaling up cancer treatment, as well as vaccination and screening

"Our findings emphasise the importance of acting immediately to combat cervical cancer on all three fronts," said Karen Canfell from the University of Sydney in Australia, who co-led both the studies.

"In just 10 years, it's possible to reduce deaths from the disease by a third and, over the next century, more than 60 million women's lives could be saved. This would represent an enormous gain in terms of both quality of life, and lives saved," Canfell said.

By adding the two screening tests, and with the treatment of precancerous cervical lesions, cases of the cancer may drop by 97 per cent, and 72 million cervical cancer cases could be averted over the next century, the researchers said.

Scaling-up of appropriate cancer treatment could avert 62 million cervical cancer deaths, the study noted.

"For the first time, we've estimated how many cases of cervical cancer could be averted if WHO's strategy is rolled out and when elimination might occur," said Marc Brisson, study co-author from Laval University.

"Our results suggest that to eliminate cervical cancer it will be necessary to achieve both high vaccination coverage, and a high uptake of screening and treatment, especially in countries with the highest burden of the disease," Brisson added.

Based on the results of the studies, WHO's cervical cancer elimination strategy has been updated which will be presented for adoption at the World Health Assembly in May 2020, the scientists noted.

"If the strategy is adopted and applied by member states, cervical cancer could be eliminated in high income countries by 2040, and across the globe within the next century, which would be a phenomenal victory for women's health," Brisson said.

"However, this can only be achieved with considerable international financial and political commitment, in order to scale-up prevention and treatment," he added.

Comments

Add new comment

  • Coastaldigest.com reserves the right to delete or block any comments.
  • Coastaldigset.com is not responsible for its readers’ comments.
  • Comments that are abusive, incendiary or irrelevant are strictly prohibited.
  • Please use a genuine email ID and provide your name to avoid reject.
News Network
February 12,2020

Washington, Feb 12: People who are optimistic may contribute to the health of their partners, staving off the risk factors leading to Alzheimer's disease, dementia and cognitive decline as they grow old together, according to a study.

The research, published in the Journal of Personality, followed nearly 4,500 heterosexual couples from the US Health and Retirement Study for up to eight years.

The researchers found a potential link between being married to an optimistic person and preventing the onset of cognitive decline, due to a healthier environment at home.

"We spend a lot of time with our partners.They might encourage us to exercise, eat healthier or remind us to take our medicine," said William Chopik, an assistant professor at the Michigan State University in the US.

"When your partner is optimistic and healthy, it can translate to similar outcomes in your own life. You actually do experience a rosier future by living longer and staving off cognitive illnesses," Chopik said.

An optimistic partner may encourage eating healthy foods, or working out together to develop healthier lifestyles, the researchers said.

For example, if a person quits smoking or starts exercising, their partner is close to following suit, they said.

"We found that when you look at the risk factors for what predicts things like Alzheimer's disease or dementia, a lot of them are things like living a healthy lifestyle," Chopik said.

"Maintaining a healthy weight and physical activity are large predictors.There are some physiological markers as well. It looks like people who are married to optimists tend to score better on all of those metrics," he said.

The researchers said there is a sense where optimists lead by example, and their partners follow their lead.

They also suggest that when couples recall shared experiences together, richer details from the memories emerge.

Chopik noted while there is a heritable component to optimism, there is some evidence to suggest that it's a trainable quality.

"There are studies that show people have the power to change their personalities, as long as they engage in things that make them change," Chopik said.

"Part of it is wanting to change. There are also intervention programs that suggest you can build up optimism," he added.

Comments

Add new comment

  • Coastaldigest.com reserves the right to delete or block any comments.
  • Coastaldigset.com is not responsible for its readers’ comments.
  • Comments that are abusive, incendiary or irrelevant are strictly prohibited.
  • Please use a genuine email ID and provide your name to avoid reject.
Agencies
May 2,2020

Clinician-scientists have found that Irish patients admitted to hospital with severe coronavirus (COVID-19) infection are experiencing abnormal blood clotting that contributes to death in some patients.

The research team from the Royal College of Surgeons in Ireland found that abnormal blood clotting occurs in Irish patients with severe COVID-19 infection, causing micro-clots within the lungs.

According to the study, they also found that Irish patients with higher levels of blood clotting activity had a significantly worse prognosis and were more likely to require ICU admission.

"Our novel findings demonstrate that COVID-19 is associated with a unique type of blood clotting disorder that is primarily focussed within the lungs and which undoubtedly contributes to the high levels of mortality being seen in patients with COVID-19," said Professor James O'Donnell from St James's Hospital in Ireland.

In addition to pneumonia affecting the small air sacs within the lungs, the research team has also hundreds of small blood clots throughout the lungs.

This scenario is not seen with other types of lung infection and explains why blood oxygen levels fall dramatically in severe COVID-19 infection, the study, published in the British Journal of Haematology said.

"Understanding how these micro-clots are being formed within the lung is critical so that we can develop more effective treatments for our patients, particularly those in high-risk groups," O'Donnell said.

"Further studies will be required to investigate whether different blood-thinning treatments may have a role in selected high-risk patients in order to reduce the risk of clot formation," Professor O'Donnell added.

According to the study, emerging evidence also shows that the abnormal blood-clotting problem in COVID-19 results in a significantly increased risk of heart attacks and strokes.

As of Friday morning, the cases increased to 20,612 cases in Ireland, with 1,232 deaths so far, according to the Johns Hopkins University.

Comments

Add new comment

  • Coastaldigest.com reserves the right to delete or block any comments.
  • Coastaldigset.com is not responsible for its readers’ comments.
  • Comments that are abusive, incendiary or irrelevant are strictly prohibited.
  • Please use a genuine email ID and provide your name to avoid reject.