Ribonucleic Acid (RNA)

RNA Translation: Protein Synthesis

rna structure

Translation is the process by which the genetic information coded in mRNA is converted into an amino acid sequence (polypeptide) through reading the mRNA coding sequence as a continuous, nonoverlapping, tri-letter code (depicted in Figure X-1, below).

This three letter- or trinucleotide code (triplets or codons) can thus be read in three possible reading frames within a single-strand mRNA molecule. The five forms of RNA play an inherent role in this translation process. Small RNAs modulate the various processes, small nuclear RNAs help to remove the introns, mRNA represents the template from which the protein is synthesized, rRNA is the cytoplasmic machine that synthesizes the protein product of the gene and tRNA donates the amino acids that are incorporated into the polypeptide during protein synthesis.

Figure X-1 | Three phases of translation
Graphic representation courtesy of Microbe Notes Opens in new window
Figure X-1 | Three phases of translation: initiation – first codon methionine; elongation – translation continues elongating the nascent peptide; termination – translation ends on recognition of the stop codon.

The tRNA molecule has a very distinct structure that is used to deliver the amino acids of the nascent polypeptide. Protein synthesis occurs on the ribosome in the cytoplasm or on ribosomes attached to cytoplasmatic side of the rough endoplasmatic reticulum membrane.

Ribosomes consist of two subunits, a 40S (small) and 60S (large), which combine to form the 80S particle. Protein synthesis begins by the formation of a complex involving a 40S ribosomal subunit carrying a methionine tRNA, which base pairs with the initiation codon AUG on the mRNA molecule.

Translation is largely regulated by controlling the formation of the initiation complex, which is the 40S ribosomal subunit, the mRNA and specific regulatory proteins.

The structure of the 5’ UTE is critical for determining whether mRNA is translated or sequestered in the untranslated ribonucleoprotein complex. Initiation of translation is also dependent on the presence of the 5’ cap structure and secondary structure of the mRNA next to the initiation codon.

Secondary structures such as stem loops in the 5’ end of the mRNA inhibit the initiation of translation. Some of the translation regulatory proteins are cell specific and mRNA specific, allowing precise post-transcriptional control over the synthesis of specific proteins. The poly(A) tail also modulates translation. Although it is not essential for translation to occur, mRNA lacking the poly(A) tail is less efficiently translated.

Once the initiation complex has formed, synthesis of the polypeptide chain is driven by the interaction between elongation factors (elFs), the ribosome and tRNA along the length of the mRNA molecule.

At each codon the ribosome and elFs promote the interaction between mRNA and tRNA.

tRNA donates an amino acid, which is added to the newly synthesized polypeptide that corresponds to the codon in the mRNA. The tRNA achieves this because it bears a triplet of bases (anti-codon) that are complementary to the mRNA codon, and there is an amino acid attached to the acceptor arm of the tRNA that corresponds to the codon in the mRNA.

When the anticodon of the tRNA matches the codon or trinucleotide sequence in the mRNA, the tRNA donates the amino acid to the newly synthesized polypeptide. For example, the first tRNA that carries methionine has the anticodon UAC; it recognizes the methionine codon AUG on mRNA.

Similarly, the anticodon AAC recognizes the leucine codon TTG on the mRNA. This process continues until the ribosome reaches a termination codon (UAA, UAG, UGA) and then the completed polypeptide is released from the ribosomal units.

Post-Translational Modification

Post-translational modification refers to the process that converts the pre-mature polypeptide into the mature protein product of the gene.

The nascent polypeptide may start to form the complex structure of the protein as it is being synthesized directly in the cytoplasm or at the membrane of the rough endoplasmic reticulum.

When formed at the ribosomes attached to the rough endosplasmatic membrane, the pre-mature polypeptide chain is likely to be transported to the Golgi body for further processing. The polypeptide may be modified further by hydroxylation, phosphorylation, glycosylation, or by proteolytic activities, which will confer functional characteristics to the protein. For example, the phosphorylation status of a protein can determine whether it is active or inactive.

See also:
  1. Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. Molecular biology of the cell. 3rd ed. New York: Garland, 1994.
  2. Darnell J, Lodish H, Baltimore D. Molecular cell biology. 2nd ed. New York: Scientific American Books, WH Freeman, 1990.