UC Berkeley

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.