Translational control (how much protein is made from one mRNA) is often exerted by regulating the initiation step, when ribosomes bind to the mRNA. In addition, recent work by many different labs has shown that the elongation phase, when the ribosome moves along the mRNA and decodes it, can also exert strong control over gene expression. We study when and why ribosome movement becomes limiting for the amount of protein that can be made, both on normal cellular mRNAs and on industrial expression constructs.
Chu D, Kazana E, Bellanger N, Singh T, Tuite MF and von der Haar T (2014) Translation elongation can control translation initiation on eukaryotic mRNAs. EMBO J 33: 21-34.
During translation, amino acids are normally incorporated into the nascent protein as determined by the sequence of codons in the translated mRNA. However, ribosomes can make mistakes at low levels, resulting in amino acid misincorporation. Depending on the site of misincorporation, this may not affect individual proteins at all, or it may reduce their activity. We are interested in how cells regulate misincorporation levels so that protein quality remains compatible with cellular function, especially under challenging conditions such as in ageing or stressed cells.
von der Haar T, Leadsham JE, Sauvadet A, Tarrant DS, Adam IS, Saromi K, Laun P, Rinnerthaler M, Breitenbach-Koller H, Breitenbach M, Tuite MF and Gourlay CW (2017) The control of translational accuracy is a determinant of healthy ageing in yeast. Open Biol, 7: 160291.
Upon release from the ribosome some proteins immediately have full activity, whereas others require the introduction of covalent modifications. Disulfide bonds are introduced by the activity of protein disuflide bond isomerases (PDI) and their associated factors, and iron sulfur clusters are introduced by specific ISC assembly pathways. On collaboration with other groups here at Kent, we study how these pathways can be adapted for the production of active recombinant proteins.