Genome complexity: control of alternate start sites (Introduction)

by Balance_Maintained , U.S.A., Tuesday, July 17, 2018, 05:52 (2322 days ago) @ David Turell

Depending the start site the coding for protein may produce a different product:

https://phys.org/news/2018-07-hidden-rnas-protein-synthesis.html

"While scanning RNAs for the first AUG, the protein-making machinery frequently encounters sites that diverge from AUG by one building block (such as AUA). On occasion, protein synthesis starts from such alternative start sites. How the protein-making machinery chooses which alternative sites to use has been a mystery.

"In a new study published in Nature, scientists describe how the protein-making machinery identifies alternative initiation sites from which to start protein synthesis. "We discovered a mechanism that explains how sites are chosen for translation events that occur in regions that are traditionally considered untranslated and that initiate at non-traditional start sites," said senior author Eckhard Jankowsky, Ph.D. "Over the last several years it has become clear that translation in these regions is pervasive, but it is poorly understood how start sites are chosen among the millions of possible start sites."

"In the new study, Jankowsky's team leveraged an enzyme that is part of the protein-making machinery—called Ded1p. Mutations in the human version of Ded1p are linked to tumors and cognitive disabilities. Viruses often target the critical enzyme to disrupt protein synthesis inside cells. Jankowsky's team created yeast cells with defective Ded1p. The use of alternative start sites for protein synthesis, like AUA or AAG, dramatically increased in these cells. However, the cells only used a small fraction of possible alternative sites.

"The researchers found that chosen alternative start sites were next to regions where the RNA folds back on itself. Ded1p is an RNA helicase—an enzyme that unzips folded RNA structures—but if it is defective it is unable to do so. If left folded, RNA structures stall scanning by the protein-making machinery and cause protein synthesis from an alternative start site nearby. "Our findings reveal a simple mechanism that involves RNA structure and a helicase." Jankowsky said. "If an alternative initiation site is close to RNA structure, it is used to start protein synthesis. So RNA structure and alternative initiation sites together are the signal to start protein production from non-traditional sites."

"Since Ded1p is present in all organisms, the findings are likely universally applicable. Protein synthesis starting from alternative translation initiation sites often impacts production of main proteins, encoded after AUG strings in the RNA, and thereby determines protein balance inside cells. "

David Comment: just another level of control which means one gene can make several different proteins.

And one that acts as a defensive mechanism for the cell, it seems. On one level, the one observed thus far, it prevents defective proteins from forming. However, the article methions that cells do this in response to viral targeting as well, which indicates to me that it might also be a low level part of the immune system. Could this be another level of viral intruder detection? If so, could the new proteins, the one generated from the alternative start site, actually act as a trigger for alerting the immune system that something got by them, and informing it of what they virus is targeting so that the immune system can respond appropriately?

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What is the purpose of living? How about, 'to reduce needless suffering. It seems to me to be a worthy purpose.