Genome complexity: hairpin RNA actions (Introduction)

by David Turell , Saturday, September 09, 2023, 21:45 (230 days ago) @ David Turell

Definitive study:

https://phys.org/news/2023-09-downstream-rna-hairpins-orchestrating-mrna.html

"Any genome is constructed with instructions that inform when to start and stop the transcription of RNA segments. These segments can contain multiple start codons, which can then be selectively used as beginning points for the ribosome to start translating them into proteins. The current study has identified a mechanism by which the selection process between potential starting points takes place.

"Ribosomal subunits assemble on an mRNA molecule and scan it for the AUG start codon to initiate protein synthesis. Sometimes, the first start codon encountered is used as initiation, and sometimes, it is not recognized. If it is not recognized, the scanning continues down the mRNA, where it may find an alternative starting point or a more easily recognized starting point (the main AUG).

"The study discovered that if the mRNA has a hairpin loop located between two starting codons, the scanning process will be slowed down, providing more time for recognition of the upstream start codon (uAUG), leading to a higher translation rate from this starting point.

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"The study identified RNA helicases, specifically RH37-like helicases, as enzymes involved in unwinding hairpin structures near uAUGs during the immune response in Arabidopsis. Elevated levels of these helicases under immune response eliminated the traffic jam caused by the hairpin, which then increased translation from the alternative start codon and thus produced a different protein.

"The "if this, then that" mechanism functions much like a logic gate, allowing the same mRNA segment to produce an alternative protein when the situation dictates.

"The researchers introduced a hairpin structure downstream of a start codon in ATF4, a well-known mammalian stress-responsive gene with higher expression levels under cellular stress conditions. This condition inhibited the translation of ATF4 through enhanced translation initiation of a less recognized start codon.

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"The experimental results demonstrate that upstream start codons and downstream hairpin structure-mediated translation initiation mechanisms are not limited to plants but are also present and functional in human cells. This suggests a universal logic gate mechanism for start-codon selection in translation initiation across different organisms with both conserved evolutionary insights and future therapeutic targeting implications.

Comment: just another complex system sowing tight controls, and more evidence for design. Also more evidence protein shape determines function.