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The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...

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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

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Synonymous codon usage influences the local protein structure observed.

Rhodri Saunders¹, Charlotte M Deane

¹Department of Statistics, Oxford University, 1 South Parks Road, Oxford OX1 3TG, UK. saunders@stats.ox.ac.uk

Nucleic Acids Research

|June 10, 2010

Summary

This summary is machine-generated.

Messenger RNA (mRNA) encodes protein structure, with codon usage and tRNA concentration influencing translation speed. Genes avoid slow codons near domain boundaries, impacting protein folding.

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Area of Science:

Molecular Biology
Bioinformatics
Structural Biology

Background:

The central dogma describes mRNA to protein translation as unidirectional.
Understanding how mRNA sequence encodes protein structure is crucial.
Existing databases lack comprehensive mapping between mRNA and protein structures.

Purpose of the Study:

To develop a database (CSandS) linking solved protein structures to their mRNA sequences.
To analyze codon usage patterns across organisms and their relation to translation speed and protein structure.
To investigate the role of translation dynamics in protein folding.

Main Methods:

Creation of the Coding Sequence and Structure (CSandS) database, mapping over 4000 protein structures to mRNA.
Analysis of codon usage frequency and tRNA concentration across various organisms.
Statistical analysis of codon usage relative to protein domain boundaries and secondary structure transitions.

Main Results:

Local protein structure information is encoded within mRNA nucleotide sequences.
tRNA concentration is a more significant determinant of translation speed than relative codon usage.
Genes avoid slow codons near domain boundaries, with translation speed decreasing at secondary structure transitions.
Specific codons exhibit structural preferences beyond amino acid encoding, varying by organism.

Conclusions:

Codons convey more information than just amino acids, influencing protein structure and folding.
Translation speed and dynamics play a significant role in the protein folding process.
The CSandS database provides a valuable resource for studying genotype-phenotype relationships at the molecular level.