1. Integrative structural biology of 3’UTRs
Supervisor: Peter Lukavsky, Dr. rer. nat.
Consultants: Boris Tichý, Ph.D., assoc. prof. Zbyněk Zdráhal
The non-coding part of the genome vastly increased from worm to humans while the number of protein-coding genes remained constant. This expansion includes 3’UTRs of mRNAs with an average length of 1.2 kb in humans and functions in mRNA transport, translational control and mRNA decay. Despite the importance of 3’UTRs for spatial and temporal control of gene expression, the molecular basis of 3’UTR functions is largely unknown. We will determine complexes of 3’UTR signals with Staufen1 protein and the ribosome which regulate mRNA stability and control translation. Using integrative structural biology approaches, including NMR spectroscopy and cryo-EM, we will unravel the molecular basis of Staufen-mediated 3’UTR functions in posttranscriptional regulation of gene expression and thus provide new insights into how deregulation can lead to diseases such as cancer and neurodegeneration. We are looking for highly motivated PhD candidates with background in biochemistry and biophysics who share our fascination for RNA-protein interactions regulating gene expression.
Sugimoto et al, Nature 2015, 519:491-4.
Yadav & Lukavsky, Prog. Nucl. Magn. Reson. Spectrosc. 2016, 97:57-81.
Gleghorn & Maquat, Trends Biochem. Sci. 2014, 39:328-40.
Keywords: Three Prime Untranslated Region, 3’UTR, mRNPs, RNA-protein networks, Staufen, RNA-based pulldown, gene expression, 3’UTR mutations, cryo EM, NMR spectroscopy