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Post-transcriptional regulation of messenger RNA

Director:
Elisa Izaurralde
Department:
Izaurralde
P-bodies in Drosophila Schneider cells

P-bodies in Drosophila Schneider cells. P-bodies are discrete cytoplasmic domains where proteins required for bulk mRNA degradation, mRNA surveillance, RNA silencing and translational repression co-localise. The image shows the co-localisation of the mRNA decapping protein DCP1 with the GW182 antigen, a P-body marker in multicellular organisms.

For close to three decades, gene expression was thought to be mainly regulated at the transcriptional level. The discovery of RNA silencing pathways, alongside the realization that post-transcriptional control provides conserved mechanisms by which cells can rapidly change gene expression patterns, have led to a renaissance in the field of post-transcriptional regulation. Post-transcriptional processes (e.g. mRNA processing, export, surveillance, silencing and turnover) are interlinked by the use of common factors and constitute a complex regulatory network that contributes to cell-type and organism specific gene expression patterns.
Our long-standing goal is the elucidation of the molecular mechanisms that regulate gene expression at the post-transcriptional level, using a combination of small-scale and functional genomic approaches.


Future projects and goals

During its entire lifespan, the mRNA acts as a platform for the binding of numerous proteins, and exists in the cell as a ribonucleoprotein particle (mRNP). It is the mRNP which is the actual substrate of post-transcriptional processes. Consequently, many RNA binding proteins play roles at multiple steps of the post-transcriptional pathway. In addition, enzymes involved in general mRNA degradation and proteins involved in mRNA surveillance, RNA silencing and translational repression, colocalise in discrete cytoplasmic foci known as mRNA processing bodies or P-bodies (see figure), suggesting that these processes are interlinked.

Our aims are:
  1. to build a comprehensive list of effectors and interaction networks for post-transcriptional pathways in order to understand how these pathways are connected with each other and with different cellular processes
  2. to determine the contribution of these post-transcriptional processes to gene expression on a  global scale and to identify endogenous targets
  3. to understand how the regulation of the endogenous targets leads to the complex phenotypes observed at the cellular and organism level when these pathways are perturbed

Scientists involved

Heike Budde
Research Scientist
Eugene Valkov
Research Scientist
Praveen Bawankar
Postdoctoral Fellow
Dipankar Bhandari
Postdoctoral Fellow
Chung-Te Chang
Postdoctoral Fellow
Cátia Igreja
Postdoctoral Fellow
Lara Wohlbold
Postdoctoral Fellow
Stefanie Becker
PhD Student
Ying Chen
PhD Student
Aoife Hanet
PhD Student
Csilla Keskeny
PhD Student
Simone Larivera
PhD Student
Sowndarya Muthukumar
PhD Student
Michelle Noble
PhD Student
Daniel Peter
PhD Student
Felix Raesch
PhD Student
Tobias Raisch
PhD Student
Vincenzo Ruscica
PhD Student
Annamaria Sgromo
PhD Student
Ramona Weber
PhD Student

Technicians
Sigrun Helms
Maria Fauser
Catrin Weiler
Min-Yi Chung