From Stanford University: ” ‘Rhythm’ of protein folding encoded in RNA, Stanford biologists find”

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Multiple RNA sequences can code for the same amino acid, but differences in their respective “optimality” slow or accelerate protein translation. Stanford biologists find optimal and non-optimal codons are consistently associated with specific protein structures, suggesting that they influence the mysterious process of protein folding.

January 29, 2013
Max McClure

“Your average musical melody doesn’t chug along at a single, mechanical speed. It mixes whole notes, quarter notes, sixteenth notes and so on to lay out a specific, complex rhythm.
It looks like protein synthesis may work the same way.

The sequence of events is elegant: proteins are assembled when match mRNA sequences up with specific tRNA molecules. Those tRNAs carry specific amino acids that link together in a chain to form a specific protein…

A hairpin loop from a pre-mRNA. Highlighted are the nucleobases (green) and the ribose-phosphate backbone (blue). Note that this is a single strand of RNA that folds back upon itself.

…But multiple RNA sequences can encode the same amino acid – some that are translated quickly, and some slowly. Although they all result in proteins with identical composition, the choice of mRNA sequence can dramatically change the rate at which the protein is made…

Protein before and after folding.

Results of protein folding.

…Research from Stanford biology Professor Judith Frydman and researcher Sebastian Pechmann now reveals that this protein synthesis “rhythm” may be evolutionarily adjusted to control the folding of the new protein chain as it emerges from the ribosome.

The finding may explain how RNA sequences define the final, folded form of a protein – a fundamental problem in molecular biology, since proteins need to fold in order to function.

‘For around 50 years, there has been a conceptual gap between the sequence and the final structure,’ said Pechmann, a postdoctoral scholar in the Frydman Lab. ‘There’s been the sense that there’s much more information in the sequence than can be deciphered at the moment.’

Published online in advance of print last month in the journal Nature Structural and Molecular Biology, the paper analyzes 10 closely related yeast species as a model. Both fast (“optimal”) and slow (“non-optimal”) codons are evolutionarily conserved, consistently appearing in particular parts of the mRNA transcript, where they appear to strategically slow down or speed up translation.

‘What they are doing is setting a tune for protein folding,’ said Frydman.”

Researchers Sebastian Pechmann and Judith Frydman. No image credit. Both researchers are affiliated with the Stanford Bio-X program.

See the full article here.

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