Post-transcriptional regulation of messenger RNA

Director:Elisa 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 BuddeResearch Scientist
Eugene ValkovResearch Scientist
Dipankar BhandariPostdoctoral Fellow
Chung-Te ChangPostdoctoral Fellow
Cátia IgrejaPostdoctoral Fellow
Lara WohlboldPostdoctoral Fellow
Aoife HanetPhD Student
Csilla KeskenyPhD Student
Yevgen LevdanskyPhD Student
Sowndarya MuthukumarPhD Student
Michelle NoblePhD Student
Felix RaeschPhD Student
Vincenzo RuscicaPhD Student
Ramona WeberPhD Student

Sigrun Helms
Maria Fauser
Catrin Weiler
Min-Yi Chung