Protein synthesis is accomplished through the process of translation of an mRNA sequence into a polypeptide chain. This process can be divided into three distinct stages: initiation, elongation and termination. During the initiation phase, the two subunits of the ribosome are brought together to the translation start site on the mRNA where the polypeptide chain is to begin. Extension of the polypeptide chain occurs when a specific aminoacyl-tRNA, as determined by the template mRNA, binds an elongating ribosome. The protein chain is released from the ribosome when any one of three stop codons in the relevant reading frame on the mRNA is reached. Individual reactions at each one of these stages are catalyzed by a number of initiation, elongation and release factors, respectively.
Proteins destined for the endoplasmic reticulum (ER) contain a short sequence of hydrophobic amino acid residues (approximately 20 residues) at their N-termini. Upon protrusion of the signal sequence from the translating ribosome, the signal sequence is bound by the cytosolic signal recognition particle (SRP), translation is temporarily halted, and the SRP:nascent peptide:ribosome complex then docks with a SRP receptor complex on the ER membrane. There the nascent peptide:ribosome complex is transferred from the SRP complex to a translocon complex embedded in the ER membrane and reoriented so that the nascent polypeptide protrudes through a pore in the translocon into the ER lumen. Translation now resumes, the signal peptide is cleaved from the polypeptide by signal peptidase as the signal peptide emerges into the ER, and elongation proceeds with the growing polypeptide oriented into the ER lumen.
The 13 proteins encoded by the mitochondrial genome are translated within the mitochondrion by mitochondrial ribosomes (mitoribosomes) at the matrix face of the inner mitochondrial membrane. Mitochondrial translation reflects both the bacterial origin of the organelle and subsequent divergent evolution during symbiosis. Mitoribosomes have shorter rRNAs, mitochondria-specific proteins, and rearranged protein positions. Mitochondrial mRNAs have either no untranslated leaders or very short untranslated leaders of 1-3 nucleotides. Translation begins with N-formylmethionine, as in bacteria, and continues with cycles of aminoacyl-tRNA:TUFM:GTP binding, GTP hydrolysis and dissociation of TUFM:GDP. All 13 proteins encoded by the mitochondrial genome are hydrophobic inner membrane proteins which are inserted cotranslationally into the membrane by an interaction with OXA1L. Translation is terminated when MTRF1L:GTP recognizes a UAA or UAG codon at the A-site of the mitoribosome. The translated polypeptide is released and MRRF and GFM2:GTP act to dissociate the 55S ribosome into 28S and 39S subunits.