The potency of RNA binding proteins as regulators of gene expression in health and disease

Dr Minni Änkö, Head - RNA Processing in Health and Disease Laboratory, Biomedicine Discovery Institute/Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC

The life and function of RNA is delicately controlled by RNA binding proteins (RBPs). These regulatory proteins are required at every step of RNA processing from transcription to translation and have immense potential to modify the gene expression output of cells. Disruption of this finely tuned regulation can have dire consequences for the cell and lead to developmental defects and diseases including cancers, underlining the importance of RBPs in gene regulation. Pluripotent stem cells display distinctive RNA processing profiles, illustrating the potentially vital role of post-transcriptional regulation in controlling pluripotency. Remarkably, embryonic stem cells (ESCs) express as many RBPs as transcription factors, yet only a few have been functionally characterized. Our work has revealed that a single RBP, SR protein splicing factor 3 (SRSF3), can control the expression of an interconnected cohort of key pluripotency factors through multiple RNA processing machineries, thus facilitating the establishment of pluripotency during reprogramming and maintenance of pluripotency in ESCs. The determination of SRSF3 activities in self-renewing cells provides insights into the essential functions of SRSF3 not only in pluripotent cells but also during early development. Furthermore, SRSF3 is a proto-oncogene and its expression is frequently dysregulated in cancer cells. The mechanisms identified in self-renewing cells have led to the identification of a novel pathway that may help elucidating the role of SRSF3 in malignant transformation. 

Minni (Minna-Liisa) Änkö heads the RNA Processing in Health and Disease Laboratory at the Biomedicine Discovery Institute/Department of Anatomy and Developmental Biology, Monash University in Melbourne. 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) until moving to her current position at the Monash University. The RNA Processing in Health and Disease Laboratory investigates gene regulation via RNA processing. Although the genome contains the code for gene expression, RNA processing tunes the output, for example through transcript variants. Thereby, RNA processing provides a critical regulatory point and aberrations in the machinery result in genetic disorders and cancer. The laboratory combines mouse genetics and developmental biology with systems biology approaches to understand how RNA binding proteins regulate gene expression in normal cells and how RNA processing defects ultimately lead to disease. Recently, the team has shown a critical role for RNA processing in orchestrating the pluripotency circuitry. Another current research focus is to uncover the role of recurring RNA processing alterations in haematological diseases.