Jiuyong Xie, Associate Professor

We are studying the regulation of alternative splicing by cell's extenal stimuli. We focus on the pre-mRNA elements and the bound splicing factors that respond to protein kinases, for example CaMK IV, important in neuronal and endocrine cell functions. Please see our Lab Research website for details.

Academic Achievements

• B.Sc. (Microbiology), Wuhan University
• Ph.D. (Genetics), Peking Union Medical College
• Postdoctoral training (Neurobiology and Molecular Biology): Cornell University and Howard Hughes Medical Institute/UCLA
• Assistant Professor, University of Manitoba, Physiology, 2003 - 2010
• Associate Professor, University of Manitoba, Physiology, 2010 - present
• CIHR New Investigator Award (2004-2009)

Research Interests:  Cell signal-regulation of alternative pre-mRNA splicing.

         Alternative splicing is a common way of gene expression regulation that can generate multiple mRNA and often protein isoforms from a single gene. More than 70% human gene transcripts are alternatively spliced and some could give rise to extremely diverse protein isoforms. This likely contributes to the proteome complexity underlying diverse protein functions, particularly in neurons and endocrine cells.  In experimental animals, genetic deficiencies in alternative splicing factors result in developmental defects or embryonic-lethal phenotypes. In humans, aberrant splicing leads to genetic diseases such as Frasier syndrome. However, it remains largely unclear how alternative splicing is controlled, particularly by cellular signals. With complex splicing patterns, widespread presence but unclear regulatory mechanisms, alternative splicing and its regulation pose a tremendous challenge in the post-genome era.

          The STREX (stress axis-regulated exon) variant of the Slo BK potassium channel gene has been used as a model to study how cell signals regulate the choice of alternative splice sites in pre-mRNAs. Inclusion of the STREX exon enhances the calcium sensitivity of BK channels and likely modulates cellular electrical properties related to hearing frequency tuning or adaptive changes in learning and memory. Its regulation by stress hormones and the calcium/calmodulin-dependent protein kinase IV (CaMK IV) makes it an interesting target for dissecting the components regulating alternative splicing as well as understanding the impact of splicing regulation on neuronal electrical properties. A first step toward this goal was made by coupling CaMK IV with a pre-mRNA element (CaRRE1) sufficient to confer CaMK IV response to an otherwise non-responsive exon. We have recently identified the splicing factor hnRNP L as an essential component of the CaMKIV-regulated splicing.

        Others being studied include exons involved in synaptic function or cell growth/apoptosis.

We hope these will help us understand how alternative splicing is regulated by cell signals in general and how this contributes to the fine-tuning of the functions of neurons and endocrine cells, as well as how mutations affect splicing in human genetic diseases.