Alain Laederach Seminar
Biology Department - University of North Carolina-Chapel Hill
"RNA Structure and Post-transcriptional Regulation of Protein Expression"
RNA is now known to be involved in many aspects of genetic regulation. An RNA's function in a cell is determined by not only its primary sequence, but also its structure. Unlike DNA, RNA rarely has a complementary second strand, so RNA nucleotides are free to interact in an intramolecular fashion resulting in folding of the polymer chain. Stretches of RNA that are complementary in sequence have a propensity to pair, forming elements of RNA secondary structure. The disruption of functional RNA structural content can be as deleterious to biological function as the disruption of functional sequence content. The consequences of these structural elements depend on their cellular context and may affect alternative splicing, poly-adenylation, RNA decay, RNA interference, regulation by long non-coding RNAs (lncRNAs) or translational efficiency. Understanding this new “code” of genetic regulation is essential to accurately predicting the relationship between protein and gene expression. By drawing on specific, human disease-phenotype associations in non-coding regions of our genome we can begin to reveal the rules that govern these relationships and better understand the potential role of RNA structure in shaping human disease and phenotype.
Alain Laederach grew up in Washington DC, received his B.S. from Ecole Polytechnique Federal de Lausanne in Chemical Engineering and received his Ph.D. from Iowa State University in Bioinformatics and Computational Biology and Chemical Engineering (co-mentors Amy Andreotti and Pete Reilly). He went on to Stanford University for a post-doc in Russ Altman’s lab in the Genetics department before starting his own lab at the University of North Carolina, Chapel Hill where he is now an associate professor in the Biology department.
The Laederach Lab’s main driving biological focus is in the field of RNA structure and function. Over the last decade, RNA has revealed itself as far more than a simple messenger of genetic information, and is now thought to play a central role in post-transcriptional regulatory processes. Since RNA is transcribed as a single strand, it folds and adopts a wide variety of structural conformations. These conformations are central components of the RNA regulatory function. They mediate interactions with other RNAs, DNA and proteins. In many cases mutation induced disruption of RNA structure will lead to phenotypic variation.
The Laederach lab predicted the existence of RNA elements, which were coined “riboSNitches” by analyzing human disease-associated mutations mapping to non-coding regions of RNAs. Since that time our lab and others have experimentally validated riboSNitches as causative elements in multiple human hereditary diseases. Most recently the lab has undertaken large-scale transcriptomic structural studies leveraging allele-specific sorting strategies to reveal the structures of RNA structure change in vivo.
Host: Walter Moss
PLEASE JOIN US AT 3:45 P.M. IN THE MBB ATRIUM FOR REFRESHMENTS