The Functions of Glycine‐rich Regions in Tdp‐43, Fus and Related Rna‐binding Proteins

Glycine‐rich regions form intrinsically unstructured domains within RNA‐binding proteins. Although they lack a defined structure when alone in solution, these domains can form more defined structural elements when interacting with other proteins or with RNA. TDP‐43 and FUS are RNA binding proteins with glycine‐rich domains that form abnormal aggregates in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The vast majority of mutations in familial ALS occur within the glycine‐rich domain of TDP‐43 as do about a third of FUS mutations. This chapter will review the various functions of some of the best characterised glycine‐rich domains in RNA‐binding proteins. Furthermore, the chapter will discuss how these findings inform on the possible functions of glycine‐rich domains in TDP‐43 and FUS.