Proteins are considered the “workhorses” of the cell and they are produced according to
the central dogma of biology. The general rule is that the genetic information hard-wired into
DNA is transcribed into a messenger RNA (mRNA) molecule which contains the program for
protein synthesis through the translation process. The regulation of protein production can
happen in many ways. The process of mRNA production (transcriptional regulation) has been
studied extensively and we have a good understanding of how it works. More recently, other
forms of regulation have been gaining attention, particularly translation initiation regulation. This
is the rate limiting step during translation and it is an important gatekeeper of protein synthesis.
This regulation occurs by both the cis-regulatory elements, which are located in the 5′- and 3′-
UTRs (untranslated regions), and by trans-acting factors. Translational control of mRNA
provides the cell with a rapid way to control changes in protein concentration and thus acts to
assist in maintaining homeostasis while also having a role in modulating more persistent
physiological changes towards cell fate (Sonnenberg and Hinnebusch, 2009). A large proportion
of the energy budget of a living cell is funneled into protein synthesis making it intimately
integrated with cell metabolism. For this reason, misregulation of translation results in
aberrations and several disease phenotypes (Silvera et al., 2010). It is therefore of great value to
understand detailed aspects of translational control when studying cell homeostasis and disease.
Untranslated regions of messenger RNAs are populated with a variety of regulatory structures
such as stem-loop structures, upstream initiation codons and open reading frames, internal
ribosome entry sites and cis-acting elements that interact with RNA-binding proteins. In the
present work, I will discuss the importance of untranslated elements on the 5’ and the 3’ ends of
specific transcripts and how interactions with these regions alter the interplay between the RNA
and the translation machinery, focusing on eukaryotic translation initiation factor eIF3,the largest
translation initiation factor.