Search form

05/03/2016 MOLIFE RESEARCH SEMINAR: Dr. Ina Huppertz

Tuesday, May 3, 2016 - 13:00
Room/Location: 
Lecture Hall of Research II

 

by

Dr. Ina Huppertz (Jacobs BCCB student 2012), now: EMBL Heidelberg, Germany

Title:

iCLIP: a versatile tool for the study of classic and enigmatic RNA-binding proteins

Ina Huppertz1,2,3, Jernej Ule2,3 and Matthias W. Hentze1

1European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, Heidelberg 69117,
Germany
2MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
3Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square,
London, WC1N 3BG, UK
 
 
RNA-binding proteins (RBPs) regulate many essential post-transcriptional processes,
such as alternative splicing, polyadenylation, mRNA localisation, translation and
degradation. In order to understand how an individual RBP can participate in a
multitude of RNA-regulatory mechanisms, a precise knowledge of their binding sites
is crucial. Individual-nucleotide resolution UV crosslinking and immunoprecipitation
(iCLIP) identifies RNA-binding sites on a genome-wide scale. This technique
uncovers RNA-binding sites with high confidence, which helps unravel the molecular
functions of both classic and enigmatic RBPs.
TDP-43 is an example of a well-studied RBP, which regulates many steps of premRNA
processing without a discernible underlying mechanism. With the help of
iCLIP and complimentary proteomic techniques, we determined how TDP43
assembles on RNA and it is involved in 3’end processing. Furthermore, we identified
that TDP43’s highly aggregation-prone protein domain inhibits its RNA binding.
The scope of iCLIP’s utility further extends to the study of enigmatic RBPs, such as
the enzymes involved in core metabolic pathways within the cell. Recently, we found
that many glycolytic enzymes bind RNA in human and yeast cells. These
observations led to a series of research questions: which RNA molecules are bound,
do different enzymes have the same set of bound targets and does the binding have a
regulatory effect? In order to address these questions, we chose ENO1, a glycolytic
enzyme, which shows reproducible RNA-binding activity in different assays and
cells. Currently, we are acquiring iCLIP data to determine the bound RNAs and their
exact binding sites.
In summary, iCLIP is a reliable tool to answer fundamental questions of the RNAbinding
of proteins.

 

 

Further information by. Prof. Dr. Sebastian Springer - Professor of Biochemistry and Cell Biology - Focus Area: Health - Life Sciences & Chemistry - Email:  s.springer [at] jacobs-university.de - Tel: +49 421 200-3243 - Link to Homepage: http://www.jacobs-university.de/ses/sspringer