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
June 22,2020

A team of scientists has produced first open source all-atom models of full-length COVID-19 Spike protein that facilitates viral entry into host cells – a discovery that can facilitate a faster vaccine and antiviral drug development.

The group from Seoul National University in South Korea, University of Cambridge in the UK and Lehigh University in the US produced the first open-source all-atom models of a full-length S protein.

The researchers say this is of particular importance because the S protein plays a central role in viral entry into cells, making it a main target for vaccine and antiviral drug development.

"Our models are the first full-length SARS-CoV-2 spike (S) protein models that are available to other scientists," said Wonpil Im, a professor in Lehigh University.

"Our team spent days and nights to build these models very carefully from the known cryo-EM structure portions. Modeling was very challenging because there were many regions where simple modeling failed to provide high-quality models," he wrote in a paper published in The Journal of Physical Chemistry B.

Scientists can use the models to conduct innovative and novel simulation research for the prevention and treatment of Covid-19.

Though the coronavirus uses many different proteins to replicate and invade cells, the Spike protein is the major surface protein that it uses to bind to a receptor.

The total number of global COVID-19 cases was nearing 9 million, while the deaths have increased to over 467,000, according to the Johns Hopkins University.

With 2,279,306 cases and 119,967 deaths, the US continues with the world's highest number of COVID-19 infections and fatalities, according to the CSSE.

Brazil comes in the second place with 1,083,341 infections and 50,591 deaths.

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News Network
February 4,2020

Toronto, Feb 4: People who text while walking face a higher risk of an accident than those listening to music or talking on the phone, a study has found.

The study, published in the journal Injury Prevention, found that smartphone texting is linked to compromised pedestrian safety, with higher rates of 'near misses', and failure to look left and right before crossing a road.

Researchers from the University of Calgary in Canada call for a more thorough approach to exploring the impact of distracted pedestrian behaviours on crash risk.

Worldwide, around 270,000 pedestrians die every year, accounting for around a fifth of all road traffic deaths, according to the researchers.

'Pedestrian distraction' has become a recognised safety issue as more and more people use their smartphones or hand held devices while walking on the pavement and crossing roads, they said.

The researchers looked for published evidence to gauge the potential impact on road safety of hand-held or hands-free device activities.

This included talking on the phone, text messaging, browsing and listening to music.

From among 33 relevant studies, they pooled the data from 14 -- involving 872 people -- and systematically reviewed the data from another eight.

The analysis showed that listening to music wasn't associated with any heightened risk of potentially harmful pedestrian behaviours.

Talking on the phone was associated with a small increase in the time taken to start crossing the road, and slightly more missed opportunities to cross the road safely.

The researchers found that text messaging emerged as the potentially most harmful behaviour.

It was associated with significantly lower rates of looking left and right before or while crossing the road, and with moderately increased rates of collisions, and close calls with other pedestrians or vehicles, they said.

Texting also affected the time taken to cross a road, and missed opportunities to cross safely, but to a lesser extent, according to the researchers.

The review of the eight observational studies revealed that the percentage of pedestrians who were distracted ranged from 12 to 45 per cent, they said.

It also found behaviours were influenced by several factors, including gender, time of day, solo or group crossing, and walking speed.

The researchers acknowledge "a variety of study quality issues" which limit the generalisability of the findings.

"Given the ubiquity of smartphones, social media, apps, digital video and streaming music, which has infiltrated most aspects of daily life, distracted walking and street cross will be a road safety issue for the foreseeable future," the researchers noted.

"And as signage and public awareness campaigns don't seem to alter pedestrian behaviour, establishing the relationship between distracted walking behaviour and crash risk is an essential research need," they said.

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Agencies
June 24,2020

New Delhi, Jun 24: Expanding the testing criterion for coronavirus, the Indian Council of Medical Research has said it should be made widely available to all symptomatic individuals across the country.

"Since test, track and treat' is the only way to prevent spread of infection and save lives, it is imperative that testing should be made widely available to all symptomatic individuals in every part of the country and contact tracing mechanisms for containment of infection are further strengthened," it said in an advisory on 'Newer Additional Strategies for COVID-19 Testing' on Tuesday.

In its revised testing strategy for COVID-19 issued on May 18, the Indian Council of Medical Research (ICMR) had advised testing for all symptomatic Influenza-like illness (ILI) among returnees and migrants within seven days of illness.

All hospitalised patients who develop ILI symptoms, symptomatic individuals living within hotspots or containment zones and healthcare and frontline workers involved in containment and mitigation of coronavirus were also advised testing.

The apex health research body has also advised authorities to enable all government and private hospitals, offices and public sector units to perform antibody-based COVID-19 testing for surveillance to help allay fears and anxiety of healthcare workers and office employees.

The earlier advisories on rapid antibody testing advisories had focused on areas reporting clusters (containment zones), large migration gatherings/evacuees centers and testing of symptomatic ILI individuals at facility level.

Besides, the ICMR on Tuesday also recommended deployment of rapid antigen detection tests for COVID-19 in combination with RT-PCR tests in all containment zones, all central and state government medical colleges and government hospitals, all private hospitals approved by the National Accreditation Board for Hospitals and Healthcare (NABH), all NABL-accredited and ICMR approved private labs, for COVID-19 testing.

All hospitals, laboratories and state governments intending to perform the point-of-care antigen tests need to register with ICMR to obtain the login credentials for data entry.

"ICMR advises all state governments, public and private institutions concerned to take required steps to scale up testing for COVID-19 by deploying combination of various tests as advised," the advisory added.

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