Reaching for the stars linking rna binding proteins to diseases

Abstract

The prototype STAR(Signal Transductionand Activation of RNA) protein is Sam68, the Src-associated substrate during mitosis of 68 kDa. Sam68, like all other STAR proteins, belongs to the large class of heteronuclear ribonucleoprotein particle K (hnRNP K) homology (KR) domain family of RNA-binding proteins. The KR domain is an evolutionarily conservedRNA binding domainthatconsists of 70-100 aminoaetds. TheKRdomain isone of the mostprevalent RNA bindingdomainsthat directly contacts single-stranded RNA with asignature topology. Sam68 contains a single KR domain that harbors additional conserved N- and C-terminal sequences also required for RNA binding specificity and dimerization. Sam68 frequently contains post-translational modifications including serine/threonine, tyrosine phosphorylation, lysine acetylation, arginine methylation and sumoylation. The phosphorylation of Sam68 or its association with 5R3 domain containing proteins has been shown to influence its RNA binding activity. Hence Sarn68 behaves as a STAR protein, whereby extacellular sia1s influence its ability to regulate RNA metabolism. Studies in mice have revealed physiological roles linking Sam68 to osteoporosis, cancer, infertility and ataxia. The role of Sam68, a closely related family member quaking (QKI), the KR domain and their links with human disease will be discussed in the present chapter. © 2010 Landes Bioscience and Springer Science+Business Media.