Dear Colleagues,

SMYD proteins are a special class of protein lysine methyltransferases with an MYND domain inserted into a SET domain. Structurally, these two functional domains are intimately bundled, with a conserved architecture, being integrated into a single coherent module in SMYD proteins. The evolutionary history of SMYD proteins dates back to more than 1 billion years ago at the beginning of multicellular life. They were found in the plant Arabidopsis thaliana, the yeast Saccharomyces cerevisiae, and Filastera, one of the closest unicellular relatives to animals. However, the nature of the selective pressure that has driven the “marriage” of the SET and MYND domains, and what specific function evolved at the time of this marriage remain unclear. From the time when SMYD1, the founding member of the SMYD protein family, was identified as being required for cardiomyocyte differentiation, our understanding of SMYD protein structure and function has been steadily increasing. We now know that not only are they involved in heart and skeletal muscle development, but they also play diverse other roles in both normal biology and disease states, ranging from tumor cell proliferation, cancer stemness and dormancy, and the immune response, to a very recent association with ciliogenesis via regulating microtubule dynamics.

While the scope of SMYD protein research has been broadened significantly over the past two decades, it is becoming increasingly clear to us that, the more we learn about the multifunctionality and multispecificity of the proteins, the more we realize that there are more yet to be discovered. With the thriving of functional genomics studies, new research ideas are emerging in uncharted areas, including but not limited to mitochondrial and nucleolar ribosome biogenesis, RNA biology in stress granules, intellectual disability, calcium-dependent signaling, and sperm chromatin remodeling at fertilization. The goal of this Special Issue is to promote new paradigms in SMYD protein research while further broadening our understanding of their functional diversity. As our knowledge develops and advances, we want to conclude that the marriage between the SET and MYND domains that made SMYD proteins so special is an ultimate rule governing their past, present and future.

Dr. Zhe Yang
Guest Editor

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• Chromatin remodeling and histone modifications
• Immunity and inflammatory response
• Intracellular trafficking and endocytosis
• RNA processing and ribosome biogenesis
• Structure and function relationships
• Heart and skeletal muscle development and cardiovascular disease
• Neurodegenerative disease and intellectual disability
• Stress response and cellular signaling
• Cell cycle regulation and telomere maintenance
• Tumor growth and metastasis