Working on this project:
mRNA translation is a universal process in every living cell, organized in a cycle that requires large and small ribosomal subunits, messenger RNA, aminoacylated transfer RNAs, and a myriad of regulatory factors. As soon as the translation machinery encounters a stop codon or stalls, termination or mRNA surveillance processes are launched. Within the CRC 902, we have identified the fundamental role of the twin-ATPase ABCE1 in ribosome recycling, which is the final – or first – step of the cyclic process of mRNA translation. In the last funding period we delineated the inner mechanics of ABCE1 during ribosome recycling and determined the structure of the ribosome-ABCE1 post-splitting complex. These studies revealed the link between termination, ribosome recycling, and initiation. In the upcoming funding period, we strive to obtain a holistic understanding of ABCE1 in mRNA translational control in Archaea and Eukarya. We aim to describe the conformational dynamics of ABCE1 during ribosome recycling, the coordinated recruitment of initiation factors and the assembly of pre-initiation complexes after ribosome splitting. We will use biochemical and biophysical approaches to arrest and delineate various ribosome-ABCE1 states in ribosome recycling and initiation. These studies will provide fundamental insights into the coupling of termination, recycling, and initiation by the recycling factor ABCE1.