题目：Study of organelle associated RNA granules in biology and disease
报告人：Weirui Ma, Ph.D.
Department of Cancer Biology and Genetics,
Memorial Sloan Kettering Cancer Center
A fundamental question in biology is how biological reactions are organized in the densely packed and highly dynamic cytoplasm. In eukaryotic cells, classic membrane-bound organelles, such as the endoplasmic reticulum (ER) and mitochondria, compartmentalize the cellular space to regulate lots of biological reactions. Also, cells have subcellular compartments made by membrane-less organelles, such as the nucleolus and stress granules, which are micron-scale structures without the surrounding lipid membrane. A major type of membrane-less organelles is RNA granules. They are formed through liquid-liquid phase separation of specific proteins and RNAs. In recent years, how membrane-less organelles are formed has come into prominence. However, to date functions of membrane-less organelles and interactions between membrane-less and membrane-bound organelles are still largely unknown. We recently discovered a new membrane-less organelle, an RNA granule called TIS granule. TIS granules assemble under physiological conditions by the RNA-binding protein TIS11B. They are gel-like and form tubule-like structures that create a reticular meshwork that is intertwined with the ER. The mesh-like shape makes TIS granules very different from so far known RNA granules which usually are sphere-like. Also, in contrast to other known membrane-less organelles, TIS granule assembly is based on a particular charge distribution pattern and is independent of the presence of an intrinsically disordered region of the protein. Besides, we found that TIS granules enrich or exclude specific proteins and mRNAs and enable the local translation of specific mRNAs at an ER subdomain. The association between TIS granules and the ER creates a subcellular compartment—the TIGER domain—with a biophysically and biochemically distinct environment from the cytoplasm. This compartment promotes 3ꞌUTR-mediated protein complex formation, thus allowing efficient surface expression of membrane proteins, including CD47 and PD-L1. Taken together, The TIS granule represents the first RNA granule that is associated with a membrane-bound organelle, the ER. These findings indicate that cells have subcellular compartment that are created through direct interactions between membrane-less and membrane-bound organelles.