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“Alternate operating manual” found in human cells under attack

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human gene CCR5/Bruce A. Shapiro and Wojciech K. Kasprzak

From ScienceDaily:

Working with a gene that plays a critical role in HIV infection, University of Maryland researchers have discovered that some human genes have an alternate set of operating instructions written into their protein-making machinery. The alternate instructions can quickly alter the proteins’ contents, functions and ability to survive.

This phenomenon, known as programmed ribosomal frameshifting, was discovered in viruses in 1985. But the UMD study, published online July 9, 2014 in the journal Nature, is the first to show that a human gene uses programmed ribosomal frameshifting to change how it assembles proteins, said senior author Jonathan Dinman, UMD professor of cell biology and molecular genetics.

In the immune system-related gene that Dinman and his colleagues studied, programmed ribosomal frameshifting triggers a process the body can use to eliminate some immune system molecules, thereby reining in potentially harmful side effects such as fever, inflammation and organ failure. The discovery could lead to better treatments for AIDS, allergies and rejection of transplanted organs, Dinman said.

It lowers the immune response to a safe level. Yet another big accident.

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Yeah, that's part's not particularly accurate, either, is it? I haven't read the full original article (it's paywalled, as usual), but according to the abstract:
A ?1 PRF event on the CCR5 mRNA directs translating ribosomes to a premature termination codon, destabilizing it through the nonsense-mediated mRNA decay pathway. At least one additional mRNA decay pathway is also involved.
...so if I'm understanding that right, other than a glitch at the frameshift, the ribosome translates it normally -- it's just that the translated protein is broken, and gets destroyed by normal broken-protein-destruction mechanisms. Gordon Davisson
From Gordon Davissons citation of the artickle:
In the case of CCR5 [the human gene found to have a programmed frameshift -GD], the frameshift changes the codons behind it into nonsense RNA. Since the ribosome can’t read them, [...]
How can there be a RNA sequence not readable by the ribosome. AFAIK any triplet RNA triplet besides the stop codon codes for an amino acid. Kajdron
"Alternate operating manual" is a bit misleading, since (in this particular case) the alternate read is nonsense. From the article:
Imagine the messenger RNA is a text made up of three-letter words (codons), spaces, and punctuation (stop codons), like this: Can any fat cat fly? To assemble proteins in the right order, the ribosome has to read all three parts of each codon, the spaces, and the stop codons. But sometimes the messenger RNA contains signals that reprogram the ribosome to jump forward or back by one or two places -- that is, to shift the frame that it is reading. This alters the text. The transfer RNA now reads either new commands to fetch completely different proteins, or meaningless, nonsense RNA, like this: Ana nyf atc atf ly? Frameshift signals are common in some viruses, which use them to cram multiple sets of commands onto a single RNA strand. Dinman has long suspected that human cells also have frameshift signals, and that they are useful. [...] In the case of CCR5 [the human gene found to have a programmed frameshift -GD], the frameshift changes the codons behind it into nonsense RNA. Since the ribosome can't read them, other components of the cell step in and destroy the messenger RNA and its associated proteins. This might seem like a bad thing. But symptoms like fever are caused by our bodies' immune response, not the underlying illness. And the immune response occasionally gets out of control, causing serious, sometimes fatal side effects. Dinman believes that by killing the messenger RNA and its array of immune system proteins, frameshifting acts like a dimmer switch, lowering the immune response to a safe level.
Gordon Davisson

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