Professor & Chairman, Department of Biochemistry, University of Texas Southwestern Medical CenterView Slides
Most DNA and RNA regulatory proteins consist of two parts. One part enables direct recognition of DNA or RNA, is well folded, and is represented by canonical domains including zinc fingers, homeoboxes, leucine zippers, RNA recognition motifs, KH domains, and pumilio domains. The other part is typified by poorly folded, low-complexity sequences whose mechanistic basis of function has long been enigmatic. When incubated at high concentration, certain of these low-complexity domains polymerize into labile, amyloid-like fibers.
My presentation will outline studies indicating that low-complexity sequence cross-beta polymers may represent the organizational basis for the formation of nuclear and cytoplasmic puncta including nuclear speckles, P granules, stress granules, and neuronal granules. It is our speculation that from the birth of a transcript in the nucleus to its ultimate translation in the cytoplasm, the entire pathway of information flow is guided by movement of the message through a solid state pathway of polymeric fibers. This “informational cytoskeleton” is regulated in a dynamic manner by post-translational modification and can be impinged upon in disease states via mutational events that enhance fiber stability.