FEB 24, 2017 2:55 PM PST

New Details About Quality Control of RNA by Cells

WRITTEN BY: Carmen Leitch

Genes are the blueprint for an organism, they contain the instructions to build functional cells. But those instructional messages in genes have to be properly interpreted and carried out by the cell. An intermediary between the genes DNA and the proteins that compose cells, is messenger RNA (mRNA) - watch the video below to learn more. Sometimes that mRNA contains errors, however, and the cell has some quality control mechanisms that can hone in on that faulty mRNA and destroy it. New research by investigators at Case Western Reserve University School of Medicine, published in Nature Communications, has outlined one such method the cell uses for identifying and taking out errors. The work indicates that the ribosome, which is responsible for the synthesis of new proteins, communicates directly with the protein complex that targets and obliterates erroneous mRNA.

 

"We aimed to understand how cells are able to recognize mRNA that is defective and distinguish it from normal mRNA. For most cells this process is critical for survival, but we didn't yet understand how it works, especially when the difference between the two is very subtle," said study leader Kristian Baker PhD, an Associate Professor in the Center for RNA Molecular Biology at Case Western Reserve University School of Medicine. "Our findings clearly show that surveillance machinery involved in identifying faulty mRNA functionally interacts with the ribosome, the apparatus responsible for synthesizing proteins in the cell. It is now clear that these two elements communicate and work closely together to recognize and eliminate aberrant mRNA from the cell."

One error that can be introduced into mRNA is a premature stop codons, so-called because they stop the ribosome short of making a full, complete protein. Such aberrant proteins can not only be non-functional, they could actually have a serious harmful effect on the cell. For this work, the research team studied the mechanisms used by the cell to find a premature stop codon and send the faulty mRNA for rapid degradation, minimizes or eliminating potential negative effects.

"Consider a car maker," said Baker. "If a faulty brake pedal sneaks past quality control and gets installed into a new car, the primary result is an improperly functioning car, which, in itself, is bad. However, failure to remove the car from the road could have grave secondary consequences if it leads to the damage of other cars, drivers or roads. Efficient quality control processes are therefore necessary, and ones that identify and remove faulty genetic intermediates from the cell are absolutely critical for avoiding downstream consequences that could negatively impact the function of the entire cell."

The investigators found that mRNAs which get stuck on premature stop codons can interact with the protein complex that watches for erroneous mRNA. That complex, UPF1, can help release the ribosome from the grips of the faulty mRNA. When UPF1 does not interact correctly with the ribosome, the damaged mRNA is not quickly degraded, which inactivates the entire surveillance system. The researchers also learned that a cellular energy source, adenosine triphosphate, can impact ribosomal function, which is a necessary part of identifying and destroying mRNA that contains premature stop codons.

The researchers hope that their work will aid in therapeutic development for genetic diseases. "About one-third of all genetic diseases involve a gene mutation that introduces a premature stop codon into the corresponding mRNA. In some cases, a therapeutic strategy that either instructs the ribosome to bypass this stop or that interferes with the recognition or elimination of the mRNA could restore some level of functional protein and lessen disease symptoms in patients," explained Baker. "What is most exciting is that once developed, such a strategy could be applied not just to a single genetic disease, but to any that occur as a consequence of these particular mutations."

Another report has also been released, also in Nature Communications, that relates to mRNA quality control in the cell. In this case, researchers led by Dr. Tarek Hilal from Charité's Institute of Medical Physics and Biophysics looked at mRNAs without any stop codons at all. They learned that these so-called non-stop mRNAs also cause the ribosome to stall. The ribosome needs assistance from proteins again to be released from these aberrant mRNAs. For this task, proteins Dom34 and Hbs1 come to the rescue, and the degradation machinery moves in on the faulty mRNA. The proteins appear to find stalled ribosomes by binding to portions of the ribosome normally occupied by mRNA. Because of competition for the binding sites, they would theoretically only be available if the mRNA was faulty.

"Research into the effects of aberrant mRNAs and the consequences of inadequate degradation is becoming increasingly significant," said Dr. Hilal. "Aberrant mRNAs have been found to be particularly common in patients with neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). Gaining an understanding of the relevant cellular control mechanisms on a molecular level may help us to develop new treatment approaches," he concluded.

You can hear more about mRNA degradation in the following talk from Howard Hughes Medical Investigator Roy Parker.

 

Sources: AAAS/Eurekalert! via Case Western Reserve University, Nature Communications Serdar et al, AAAS/Eurekalert via Charité - Universitätsmedizin Berlin, Nature Communications Hilal et al 

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
OCT 22, 2021
Genetics & Genomics
Studying the Evolution of SARS-CoV-2 in One Patient Over 324 Days
OCT 22, 2021
Studying the Evolution of SARS-CoV-2 in One Patient Over 324 Days
To clear a viral infection, the human body has to mount an effective immune response. After detecting the pathogen, immu ...
NOV 01, 2021
Cell & Molecular Biology
How SARS-CoV-2 Evades Antiviral Defenses
NOV 01, 2021
How SARS-CoV-2 Evades Antiviral Defenses
Researchers have learned a lot about the SARS-CoV-2 virus since the start of the COVID-19 pandemic. We know that he viru ...
NOV 11, 2021
Health & Medicine
The Taconic-Cyagen Academic Model Generation Alliance
NOV 11, 2021
The Taconic-Cyagen Academic Model Generation Alliance
With more than 15 years of experience in genetic engineering, Cyagen utilizes a highly efficient process, including prop ...
NOV 07, 2021
Cell & Molecular Biology
How Cells Use Messengers to Signal to One Another
NOV 07, 2021
How Cells Use Messengers to Signal to One Another
In recent years, researchers have discovered the importance of a kind of antenna that is found on most cells, a structur ...
NOV 19, 2021
Health & Medicine
Introducing the Human Proteoform Project
NOV 19, 2021
Introducing the Human Proteoform Project
First, there was the Human Genome Project, a monumental, international effort to map the entire human genome down to its ...
NOV 19, 2021
Cell & Molecular Biology
Viral RNA Can Hijack the Host by Assuming a tRNA-Like Structure
NOV 19, 2021
Viral RNA Can Hijack the Host by Assuming a tRNA-Like Structure
Many viruses have genomes made of RNA. In human cells, messenger RNA (mRNA) molecules act as intermediates; cellular mac ...
Loading Comments...