Abstract
Translation of messenger RNA (mRNA) in bacteria occurs in the steps of
initiation, elongation, termination and ribosome recycling. The
initiation step comprises multiple stages and uses a special transfer
RNA (tRNA) called initiator tRNA (i-tRNA), which is first aminoacylated
and then formylated using methionine and N
10-formyl-tetrahydrofolate (N
10-fTHF), respectively. Both methionine and N
10-fTHF are produced via one-carbon metabolism,
linking translation initiation with active cellular metabolism. The
fidelity of i-tRNA binding to the ribosomal peptidyl-site (P-site) is
attributed to the structural features in its acceptor stem, and the
highly conserved three consecutive G-C base pairs (3GC pairs) in the
anticodon stem. While the acceptor stem region is important in
formylation of the amino acid attached to i-tRNA and its initial binding
to the P-site, the 3GC pairs are crucial in transiting i-tRNA through
various stages of initiation. We utilized the feature of 3GC pairs to
investigate the nuanced layers of scrutiny that ensure fidelity of
translation initiation through i-tRNA abundance and its interactions
with the components of the translation apparatus. We discuss the
importance of i-tRNA in the final stages of ribosome maturation, as also
the roles of the Shine-Dalgarno sequence, ribosome heterogeneity,
initiation factors, ribosome recycling factor and coevolution of the
translation apparatus in orchestrating a delicate balance between the
fidelity of initiation and/or its leakiness to generate proteome
plasticity in cells to confer growth fitness advantages in response to
the dynamic nutritional states.