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
February 6,2020

Researchers have found the rates of lung cancer are higher in young women than men.

The study, published in the journal Pediatrics, examined lung cancer rates in young adults in 40 countries across five continents and uncovered a trend of higher lung cancer rates in women compared with men in recent years.

The emerging trend was widespread, affecting countries across varied geographic locations and income levels.

The changes appeared to be driven by a rising rate of adenocarcinoma lung cancer among women, said the study researchers from University of Calgary in Canada.

Lung cancer rates have been higher among men than women because men started smoking in large numbers earlier and smoked at higher rates; however, recent studies have reported converging lung cancer incidence rates between sexes.

Among men, age specific lung cancer incidence rates generally decreased in all countries, while in women the rates varied across countries with the trends in most countries stable or declining, albeit at a slower pace compared to those in men.

For the findings, lung and bronchial cancer cases between 30-64 age group from 1993-2012 were extracted from cancer incidence in five continents.

The study found the higher emerging rates of lung cancer in young women compared to young men.

According to the researchers, future studies are needed to identify reasons for the elevated incidence of lung cancer among young women.

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Agencies
May 17,2020

Geneva, May 17: Spraying disinfectant on the streets, as practised in some countries, does not eliminate the new coronavirus and even poses a health risk, the World Health Organization (WHO) warned on Saturday.

In a document on cleaning and disinfecting surfaces as part of the response to the virus, the WHO says spraying can be ineffective. "Spraying or fumigation of outdoor spaces, such as streets or marketplaces, is... not recommended to kill the Covid-19 virus or other pathogens because disinfectant is inactivated by dirt and debris," explains the WHO.

"Even in the absence of organic matter, chemical spraying is unlikely to adequately cover all surfaces for the duration of the required contact time needed to inactivate pathogens." The WHO said that streets and pavements are not considered as "reservoirs of infection" of Covid-19, adding that spraying disinfectants, even outside, can be "dangerous for human health".

The document also stresses that spraying individuals with disinfectants is "not recommended under any circumstances".

"This could be physically and psychologically harmful and would not reduce an infected person's ability to spread the virus through droplets or contact," said the document.

Spraying chlorine or other toxic chemicals on people can cause eye and skin irritation, bronchospasm and gastrointestinal effects, it adds.

The organisation is also warning against the systematic spraying and fumigating of disinfectants on to surfaces in indoor spaces, citing a study that has shown it to be ineffective outside direct spraying areas.

"If disinfectants are to be applied, this should be done with a cloth or wipe that has been soaked in disinfectant," it says.

The SARS-CoV-2 virus, the cause of the pandemic that has killed more than 300,000 people worldwide since its appearance in late December in China, can attach itself to surfaces and objects.

However, no precise information is currently available for the period during which the viruses remain infectious on the various surfaces.

Studies have shown that the virus can stay on several types of surfaces for several days. However, these maximum durations are only theoretical because they are recorded under laboratory conditions and should be "interpreted with caution" in the real-world environment.

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News Network
July 10,2020

Toronto, Jul 10: Pasteurising breast milk at 62.5 degrees Celsius for 30 minutes inactivates the SARS-CoV-2 virus that causes Covid-19, making it safe for consumption by babies, a study claims.

According to the research published in the Canadian Medical Association Journal, current advice for women with Covid-19 is to continue to breastfeed their own infants.

In Canada, it is standard care to provide pasteurised breast milk to very-low-birth-weight babies in hospital until their own mother's milk supply is adequate, the researchers said.

"In the event that a woman who is Covid-19-positive donates human milk that contains SARS-CoV-2, whether by transmission through the mammary gland or by contamination through respiratory droplets, skin, breast pumps and milk containers, this method of pasteurisation renders milk safe for consumption," said Sharon Unger, a professor at the University of Toronto in Canada.

The Holder method, a technique used to pasteurise milk in all Canadian milk banks at 62.5 degrees Celsius for 30 minutes, is effective at neutralising viruses such as HIV, hepatitis and others that are known to be transmitted through human milk, the researchers said.

In the latest study, the researchers spiked human breast milk with a viral load of SARS-CoV-2 and tested samples that either sat at room temperature for 30 minutes or were warmed to 62.5 degrees Celsius for 30 minutes.

They then measured for active virus, finding that the virus in the pasteurised milk was inactivated after heating.

More than 650 human breast milk banks around the world use the Holder method to ensure a safe supply of milk for vulnerable infants, the researchers said.

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