The RNA structure Simko and colleagues studied was the G-quadruplex, a four-stranded structure formed by guanine-rich RNA. “We noticed that a group of related proteins display binding preference for a particular RNA structure and wondered if this mode of binding could contribute to the recruitment of these proteins to the long non-coding RNA NEAT1,” a key step in paraspeckle formation, said Simko. But scientists didn’t know what elements mediated the interactions between NEAT1 lncRNA and its key protein partners, although some researchers hypothesized that three-dimensional structures could play a role. Each paraspeckle consists of approximately 50 NEAT1 ribonucleoprotein particles. The paraspeckles themselves are built on a physical scaffolding of a long non-coding RNA, or lncRNA, called NEAT1. They play a role in a variety of physiological processes, including those in the nervous system and in fertility in females. Paraspeckles are found in the nucleus and are believed to help control gene expression through diverse pathways. Pathologies in paraspeckles have been found in neurodegenerative diseases,” said Wang. “Paraspeckles remain an enigmatic organelle that provides a fascinating model for studying formation of membraneless bodies. Wang described this work as part of his lab’s interest in both the fundamental biology of RNA and protein homeostasis and their potential implications in human diseases. The research was led by Eric Simko, a recent PhD graduate from the lab who is now a postdoctoral fellow at the National Cancer Institute’s RNA Biology Laboratory. In a new study in Nucleic Acids Research from the lab of Jiou Wang, PhD, associate professor in the Department Biochemistry and Molecular Biology, showed that RNA structures called G-quadruplexes play a role in the formation and function of a type of granule called a paraspeckle. Unlike membrane-bound organelles, these bodies or granules are not surrounded by a membrane but held together by biochemical and physical interactions between the RNA and protein building blocks. As scientists have delved deeper into the biology of cell dynamics and human diseases, one of the processes that continue to emerge is the formation and disassembly of membraneless organelles-bodies of concentrated RNA and protein.
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