From cells to systems – Deciphering RNA regulation in stem cells and cancer

Although the DNA contains the code for gene expression, RNA processing tunes the output because newly transcribed RNAs are not functional but need to undergo tightly regulated processing steps such as pre-mRNA splicing and polyadenylation. RNA processing provides a critical regulatory point and aberrations in the RNA processing machinery result in genetic disorders and are linked to cancer. The molecular mechanisms that bring about specific cellular RNA repertoires and drastic RNA aberrations in disease are not well understood. Thus, understanding the cellular relevance of RNA processing remains a major challenge in the field. It is clear that RNA binding proteins (RBPs) play a critical role in defining cellular RNA repertoires by delicately controlling the life of all coding and noncoding RNAs.

Our work focuses on investigating how RNA-protein interactions regulate gene expression through RNA processing in specific tissues and in disease. By taking a ‘functional RNAomics’ approach, we have uncovered how the RNA binding protein SRSF3 regulates coordinated RNA networks depending on the cellular environment. In pluripotent cells, SRSF3 controls the processing of both coding and non-coding RNAs to govern the ‘stemness’ properties of self-renewing cells. However, ‘stemness’ has both good and bad aspects. Our work in pluripotent cells has led to a discovery of an SRSF3 mediated RNA processing program that is characteristic of poorly differentiated stem cell like tumours. Thus, the combination of genomics and bioinformatics with cell biology and molecular biology enables us linking molecular level events to cellular functions which will help in deciphering the RNA code of different cell types and has major implications in disease biology.

Minni (Minna-Liisa) Änkö heads the RNA Biology in Health and Disease Laboratory at the Hudson Institute of Medical Research. She obtained her PhD from the Åbo Akademi University in Finland. She was a post-doctoral fellow at the Max Planck Institute of Cell Biology and Genetics, in Dresden, Germany 2006-2011. Minni moved to Australia in 2011, when she worked as a visiting scientist at the Australian Regenerative Medicine Institute, Monash University. She then continued her research as a senior research fellow at the Walter and Eliza Hall Institute (2012-2013). She established her independent laboratory at Monash University in 2014 and recently moved to her current position at the Hudson Institute. The RNA Biology in Health and Disease Laboratory investigates gene regulation via RNA processing by combining wet and dry lab approaches.  The focus is on understanding how RNA binding proteins tune gene expression output in various types of stem cells and the haematopoietic system and how aberrations in the machinery result in genetic disorders and cancer.