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Whether in Bacteria or Humans, Quality Control Systems Operate Everywhere in the Cell

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Search for the phrase “quality control” in our pages and you will find a lot of entries. Both words, “quality” and “control,” fit a model of intelligent design beautifully.

By contrast, why would an unguided Darwinian process care about “quality”? Why would evolution care about “control”? That’s especially the case where the two occur in combination. The phrase presupposes a mindful goal of controlling quality. It’s always satisfying, therefore, to find these loaded terms in scientific literature, where you notice that invocations of the phrase are inversely proportional to mentions of “evolution.” Fancy that.

Let’s look at some papers that specifically use the phrase “quality control.”

1. “Direct Communication between Cell’s Surveillance and Protein Synthesizing Machinery Eliminates Genetic Errors” (Case Western Reserve University). The news item combines ID-friendly concepts of surveillance, communication, synthesizing machinery, and error correction. Here’s the phrase we’re looking for: “New research out of Case Western Reserve University School of Medicine describes a mechanism by which an essential quality control system in cells identifies and destroys faulty genetic material.”

In their work, they ask: how can a cell distinguish between normal messenger RNA and defective mRNA? They describe “evidence for direct communication between the cell’s protein synthesis machinery — the ribosome — and the protein complex that recognizes and destroys defective genetic intermediates called messenger RNAs (mRNAs).” Direct communication; that’s pretty neat. Read all about it in Nature Communications, an open-access journal, which also uses the phrase “quality control.” We must share this nifty analogy from the news announcement:

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.”

2. Researchers from Hungary published this paper in the Proceedings of the National Academy of Sciences (PNAS): “Shuttling along DNA and directed processing of D-loops by RecQ helicase support quality control of homologous recombination.” The phrase also appears ten times in the body of the paper. The team studied RecQ helicase, one of several enzymes in bacteria and humans that ensure quality control of DNA repair by homologous recombination. It’s amazing to find an enzyme that can distinguish between good and bad recombination events and take action.

A major role suggested for RecQ is the selective inhibition of illegitimate recombination events that could lead to loss of genome integrity. How can RecQ enzymes perform an exceptionally wide range of activities and selectively inhibit potentially harmful recombination events? Here, we propose a model in which the conserved domain architecture of RecQ senses and responds to the geometry of DNA substrates to achieve HR quality control.” [Emphasis added.]

In the Abstract, the researchers state that DNA damage is inevitable. Cells must continually repair damage “while avoiding the deleterious consequences of imprecise repair,” they say. They proposed a model that implicates the geometry of DNA “through which RecQ helicases achieve recombination precision and efficiency.”

3. Another paper in PNAS by two researchers from Howard Hughes Medical Institute finds that “Quality control mechanisms exclude incorrect polymerases from the eukaryotic replication fork.” They first describe DNA replication as “a central life process and is performed by numerous proteins that orchestrate their actions” to produce two identical copies of the genome before cell division. Notice that they suspect a rational cause behind a mystery:

While the antiparallel architecture of DNA is elegant in its simplicity, replication of DNA still holds many mysteries. For example, many essential replication proteins still have unknown functions. In eukaryotes the two DNA strands are duplicated by different DNA polymerases. The mechanism by which these different polymerases target to their respective strands is understood. This report examines the mechanisms that eject incorrect polymerases when they associate with the wrong strand.

4. Nature published a paper by researchers at the University of Göttingen: “mRNA quality control is bypassed for immediate export of stress-responsive transcripts.” We know from human civilization that sometimes you have to sacrifice one good for a greater good — like survival. A government may have to suspend standard procedures in wartime, for instance, in order to rush ammunition to the front lines. Something like that goes on in cells, which often enter stressful situations.

Cells grow well only in a narrow range of physiological conditions. Surviving extreme conditions requires the instantaneous expression of chaperones that help to overcome stressful situations. To ensure the preferential synthesis of these heat-shock proteins, cells inhibit transcription, pre-mRNA processing and nuclear export of non-heat-shock transcripts, while stress-specific mRNAs are exclusively exported and translated.

We can relate to the analogy with wartime, but how does a cell know to let the emergency responders through? They found that the rules for adaptors change. Non-stress transcripts lose their adaptors so that they cannot be exported. Simultaneously, stress proteins get relaxed permission to exit the gates and get to work. Notice three uses of the phrase “quality control’ in this excerpt:

An important difference between the export modes is that adaptor-protein-bound mRNAs undergo quality control, whereas stress-specific transcripts do not. In fact, regular mRNAs are converted into uncontrolled stress-responsive transcripts if expressed under the control of a heat-shock promoter, suggesting that whether an mRNA undergoes quality control is encrypted therein. Under normal conditions, Mex67 adaptor proteins are recruited for RNA surveillance, with only quality-controlled mRNAs allowed to associate with Mex67 and leave the nucleus. Thus, at the cost of error-free mRNA formation, heat-shock mRNAs are exported and translated without delay, allowing cells to survive extreme situations.

Now let’s briefly look at a few more papers that imply quality control without explicitly using the phrase.

5. “Acetylation promotes TyrRS nuclear translocation to prevent oxidative damage” (PNAS). Chinese scientists investigated a post-translational modification to Tyrosine tRNA synthetase. This particular member of the synthetase family has a second job: protecting the nucleus against oxidative stress. An acetyl tag lets it relocate to the nucleus, something like a badge that can let a volunteer firefighter get past the traffic cops and through the crowds. “Herein, we report that TyrRS becomes highly acetylated in response to oxidative stress, which promotes nuclear translocation.” Here’s another bragging right for the twenty-member enzyme family: “many aminoacyl-tRNA synthetases, including TyrRS, have been shown to take on multiple roles.”

6. “First-passage time approach to controlling noise in the timing of intracellular events” (PNAS). Timing is another key concept in quality control. In this paper from the University of Delaware, three researchers ask how the cell can keep order in a noisy environment. “Understanding how randomness in the timing of intracellular events is buffered has important consequences for diverse cellular processes, where precision is required for proper functioning.” The insights they gain from experiment involve critical levels, feedback regulation, and event triggers. “Formulas shed counterintuitive insights into regulatory mechanisms essential for scheduling an event at a precise time with minimal fluctuations.” That’s quality control.

7. “Study characterizes key molecular tool in DNA repair enzymes” (Science Daily). From the University of North Carolina at Charlotte come revelations about a component of DNA repair enzymes dubbed Zf-GRF, “which is highly conserved in several enzymes and across species, [and] has been shown to be a key molecular tools [sic] that binds and orients repair enzymes to DNA.” Repair, naturally, is a key concept in quality control design. The paper, “APE2 Zf-GRF facilitates 3′-5′ resection of DNA damage following oxidative stress,” is published by PNAS.

8. “Histone degradation accompanies the DNA repair response” (Friedrich Miescher Institute for Biomedical Research). Human rapid-response teams need assistants. How well would paramedics operate, for example, without dispatchers and vehicle technicians? The news item for a paper in Nature Structural & Molecular Biology describes quality control of this sort without using the phrase:

DNA repair is paramount for the functioning of every cell and organism. Without it, proteins no longer work properly and genes are misregulated, all of which can lead to disease. It comes therefore as no surprise that the cell devotes enormous resources to detect and repair DNA damage and ensure DNA integrity.

Pretty clear, isn’t it? Quality control operates at every level and every location in the cell. By logical implication, so does intelligent design.

Photo: Quality control inspector, sewing machine parts factory, Dresden, 1977, by Deutsche Fotothek‎ [CC BY-SA 3.0 de], via Wikimedia Commons.