Anyone who has taken a biology or biochemistry class is familiar with the central dogma of the biological sciences, which describes the flow of genetic information. It dates back to Francis Crick in 1956 and can be simplified to the following concept: DNA encodes for RNA, and RNA encodes for proteins.

alzheimers word cloud with other words like healthA new study1 from the University of Utah reveals that this linear flow of information might not be as straightforward as we once thought.
The study takes a close look at the quality control process involved in protein synthesis. Protein-making machines known as ribosomes are responsible for stitching together the amino acid building blocks of proteins by using the sequence of messenger RNA (mRNA) as a blueprint.

When an error occurs, the ribosome will stall. This recruits an assembly of proteins charged with disassembling the ribosome, removing the faulty RNA and degrading the improperly made protein.
One particular quality control protein, known as Rqc2p, was found to play a surprising role. This protein — which is conserved across numerous species, from yeast to humans — binds to the stalled ribosome and promotes the continuation of protein synthesis without the use of the template mRNA sequence. Rqc2p accomplishes this unique function by binding to transfer RNA (tRNA) molecules carrying alanine or threonine amino acids.

The binding of specific tRNAs to the ribosome is generally facilitated by the sequence of the mRNA, but this protein manages to bypass what was once perceived as a crucial step in the protein-making process. This results in a nonsensical tag of alanines and threonines added to the end of improperly made proteins.
One potential purpose of this tag may be to target the dysfunctional protein for degradation. Accumulation of degenerate proteins has been linked to neurodegenerative diseases, such as Alzheimer’s and Huntington’s. The study authors suggest this new method of protein synthesis could contribute to disease prevention.

Peter Shen, Ph.D., and co-authors first arrived at this interesting finding when they used cryo-electron microscopy to determine the structure of the quality control proteins bound to a stalled ribosome. They observed that Rqc2p was bound to both the ribosome and a tRNA, which it had positioned adjacent to the improperly made protein chain. Seeing is not always believing, though, so the scientists involved in the study carried out numerous biochemical assays to validate this new method of protein synthesis.

The next steps will be to determine when this process takes place in the grand scheme of the cell cycle and what occurs when this process fails. While those key points are still unclear, what we know for sure is that our notion of how nature works is far more complicated than once perceived, and that old dogmas are subject to change with time and innovation.
The study was published in the Jan. 2, 2015, edition of Science

 

1. Rcq2p and 60S ribosomal subunits mediate mRNA-indpendent elongation of nascent chains. Peter S. Shen, Joseph Park, Yidan Qin, Xueming Li, Krishna Parsawar, Matthew H. Larson, James Cox, Yifan Cheng, Alan M. Lambowitz, Jonathan S. Weissman, Onn Brandman, Adam Frost. Science. Jan. 2, 2015: Vol. 347 no. 6217 pp. 75-78.

About the Author

Shannen Cravens

Shannen Cravens is a Ph.D. student in molecular biophysics with a passion for teaching who enjoys weaving art into her lab life.

While we’ve all heard the tired warning to wear our coats outside so we don’t get sick, it’s fair to wonder how much validity there is to such reasoning. Are we really more likely to catch a cold in colder weather?

woman sneezing

Lucky for us, scientists at Yale are looking into it. Their recent article1, published in Proceedings of the National Academy of Sciences, looked at the effect that colder temperatures had on rhinovirus growth in mouse airway epithelial cells (AECs). It was already known that rhinoviruses grow better at cooler temperatures — around 33 degrees Celsius — but the mechanisms by which this preferential growth occurred remained largely unknown. However, in this article, scientists presented new findings that suggest the mechanism is more related to impaired immune function in the infected cells than directly virus intrinsic.

Specifically, the researchers used ex vivo treatment of mouse AECs infected with a mouse-adapted rhinovirus to test differences in cellular processes at varying temperatures.

When compared to those cells grown at 37 degrees Celsius, the cells grown at 33 degrees Celsius had a significantly decreased amount of immune response elements, including both type 1 and type 3 interferon subtypes and interferon-stimulated genes.

Intriguingly, it is known that interferons limit viral growth and have been specifically reported to limit rhinovirus growth2, and interferon-stimulated genes are known to aid in immune response to viruses.

Taken together, these findings provide a potential mechanism by which growth of rhinovirus might be inhibited at higher temperatures. The paper goes on to further elucidate cellular mechanisms for this differential interferon production. Specifically, the researchers discovered that the recognition of viral replication intermediates, namely, dsRNA, by RIG-I-like receptors (RLRs), was responsible for the increased interferon response at higher temperatures. RLRs are part of our innate immune system and are responsible for recognition of “nonself” antigens, such as viral RNA.

But how is the temperature difference affecting the interferon response? Through a series of experiments, the researchers identified two mechanisms that affect viral growth at differing temperatures. Essentially, they found that at 33 degrees Celsius, decreased RLR enzyme activity was responsible for the less potent interferon response. At 37 degrees Celsius, enhanced signaling through type 1 interferon receptors resulted in increased interferon production.

The the authors’ findings suggest there is a temperature-based growth advantage in cells infected with rhinovirus, and this advantage is mediated through cell-intrinsic mechanisms. While more research is needed, this study could help explain why cold temperatures could lead to more cases of the cold virus.

 

1 Foxman EF, et al. (2015) Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells. Proc Natl Acad Sci USA [Epub ahead of print].
2 Becker TM, et al. (2013) Exogenous interferons reduce rhinovirus replication and alter airway inflammatory responses. Ann Allergy Asthma Immunol 111(5):397–401.

About the Author

Bree Yanagisawa

Bree Yanagisawa is an aspiring scientist who is passionate about the unique opportunity represented in engaging science through the use of mass media sources.

In a year where scientists have turned back the clock on aging and designed robots to think as a group, choosing a standout success is a charge that is near impossible.

However, when Science magazine released its annual short list of the most outstanding contributions to the scientific field, it ultimately made the difficult decision of naming the Breakthrough of the Year. From the 19 exceptional candidates of the past year, one soared high above the rest. The 2014 Breakthrough of the Year is the landing of Philae on Comet 67P/Churyumov-Gerasimenko.

The descent is a feat 10 years in the making, and the exciting trek of the lunar lander appears borrowed from the pages of science fiction novels. The project, spearheaded by the European Space Agency with a price tag of 1.4 billion euros, began with the launch of the Rosetta vessel in 2004. Over the next decade, Rosetta was flung through the orbits of Earth and Mars, gaining the momentum necessary to align with the 6.5-year orbit of the Comet 67P. Once Rosetta entered the orbit of 67P, scientists could breathe a sigh of relief.

The entry marked a first in the history of space travel and meant the mission was on the whole a success, as Rosetta itself contains most of the payload for the discovery portion of the launch. Because Rosetta is trapped in the orbit of 67P, sometimes nearing 10 kilometers from the surface, the comet's movements can be tracked for the foreseeable future. Onboard are powerful spectrometers and instruments with the capability to scan the comet visually and analyze the composition of its atmosphere. These two pieces of data will give scientists the ability to postulate on the comet’s formation billions of years ago, ultimately providing some answers to our universe’s origin.

After relaxing into orbit, Rosetta’s next daunting mission was to launch the Philae lander. Researchers watched nervously as Philae emerged from Rosetta and made its seven-hour journey to 67P. Philae neared the surface in what should have been a perfect entrance, but for reasons unknown, its rear thrusters and anchoring harpoons failed to attach the tiny lander into the ground of the comet. Instead, Philae bounced around in the low-gravity environment, causing fear of its loss to the depths of space.

In the end, Philae stuck its landing, albeit in the darkened shadow of rocks. Since the solar panels couldn’t be effectively recharged, scientists had 57 hours of battery life to conduct their groundbreaking measurements. Data from the first science sequence was transmitted from Philae to Rosetta and eventually to the mission headquarters before Philae powered down, finding solid ice, a vast amount of dust and a rich array of organic molecules. Further analysis is needed to validate the findings, but the crew is optimistic.

Philae’s beloved Twitter account ends this nail-biting saga on a hopeful note about its future activity: “My #lifeonacomet has just begun @ESA_Rosetta. I'll tell you more about my new home, comet #67P soon… zzzz #CometLanding.”

About the Author

Kirstie Keller

Kirstie Keller is a classically trained ballerina-turned-scientist with a penchant for 90s music. She enjoys piecing together the details of a discovery into the larger puzzle of life.