Translation: The Genetic Code and Protein Synthesis

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Translation: The Genetic Code and Protein Synthesis

Central Dogma and Translation Overview

The central dogma of molecular biology describes the flow of genetic information from DNA to RNA to protein. Translation is the process by which the nucleotide sequence of messenger RNA (mRNA) is converted into the amino acid sequence of a protein.

Transcription: DNA is transcribed into mRNA.
Translation: mRNA is translated into a polypeptide (protein).
Codon: A sequence of three nucleotides in mRNA that specifies an amino acid.

Codons and the Genetic Code

The genetic code is composed of codons, each consisting of three nucleotides (A, U, C, G in RNA). Each codon corresponds to a specific amino acid or a stop signal during translation.

SENSE DNA (coding strand): The DNA strand whose sequence matches the mRNA (except T is replaced by U).
ANTISENSE DNA (template strand): The DNA strand complementary to the mRNA.
Codon Choices: Four possible nucleotides (A, U, C, G) yield 64 possible codons.
Start Codon (AUG): Specifies methionine (Met); all proteins begin with Met.
Stop Codons: UAA, UAG, UGA signal termination of translation.

Example: Codon Table

Codon	Amino Acid
AUG	Methionine (Start)
UUU	Phenylalanine
UAA	Stop
GCU	Alanine
Additional info: ...	Other codons specify remaining amino acids

Polypeptide Structure and Peptide Bond Formation

Proteins are polymers of amino acids linked by peptide bonds. Each polypeptide has polarity, with an N-terminus (amino end) and a C-terminus (carboxyl end).

Peptide Bond: Formed between the carboxyl group of one amino acid and the amino group of the next.
Directionality: Polypeptides are synthesized from the N-terminus to the C-terminus.

Peptide Bond Formation Equation:

Sequence is written from the amino (N) to the carboxyl (C) terminus.

Translation Machinery: Components and Function

Translation requires several key components:

mRNA: Provides the codon sequence to be translated.
tRNA: Adaptor molecules that carry specific amino acids and recognize codons via their anticodon loop.
Ribosome: Large ribonucleoprotein complex that catalyzes peptide bond formation and coordinates translation.

Ribosome Structure

Prokaryotic Ribosome: 70S (composed of 50S large and 30S small subunits)
Eukaryotic Ribosome: 80S (composed of 60S large and 40S small subunits)
Svedberg Unit (S): Measures sedimentation rate; not additive.

Organism	Ribosome	Large Subunit	Small Subunit
Prokaryote	70S	50S	30S
Eukaryote	80S	60S	40S

Translation Process: Initiation, Elongation, Termination

Translation occurs in three main stages:

Initiation

Ribosome assembles at the start codon (AUG) on mRNA.
Initiator tRNA carrying methionine binds to the start codon.
Initiation factors (IFs in prokaryotes, eIFs in eukaryotes) facilitate assembly.

Elongation

tRNA enters the A site of the ribosome, matching its anticodon to the mRNA codon.
Peptide bond forms between the growing polypeptide and the new amino acid.
Ribosome translocates, moving the tRNA and mRNA by one codon.

Termination

Stop codon is reached; release factors promote dissociation of the ribosome and release of the polypeptide.

tRNA Structure and Function

tRNA: Has a cloverleaf secondary structure and L-shaped tertiary structure.
Anticodon: Region that base-pairs with the mRNA codon.
Aminoacyl-tRNA synthetase: Enzyme that attaches the correct amino acid to its tRNA; there are 20 such enzymes.

Translation Sites in the Ribosome

A site (Aminoacyl): Entry site for new aminoacyl-tRNA.
P site (Peptidyl): Holds the tRNA with the growing polypeptide chain.
E site (Exit): Site where uncharged tRNA exits the ribosome.

Special Features and Differences: Prokaryotes vs Eukaryotes

Prokaryotes: Shine-Dalgarno sequence helps ribosome recognize start site; mRNAs can be polycistronic (multiple proteins from one mRNA).
Eukaryotes: Ribosome recognizes the 5' cap and scans for the first AUG in a favorable context (Kozak sequence); mRNAs are typically monocistronic.

Summary Table: Key Differences in Translation Initiation

Feature	Prokaryotes	Eukaryotes
Start Site Recognition	Shine-Dalgarno sequence	5' cap and Kozak sequence
Initiation Factors	3 IFs	>12 eIFs
Polycistronic mRNA	Yes	No
First Amino Acid	Formyl-methionine	Methionine

Additional info:

Some details inferred from context and standard genetics knowledge, such as the full codon table and the role of aminoacyl-tRNA synthetases.
Peptide bond formation is catalyzed by the ribosome's peptidyl transferase activity, which is a ribozyme function of the large subunit rRNA.