DOES SINE EVOLUTION PRECLUDE ALU FUNCTION

The evolution, mobility and deleterious genetic effects of human Alus are fairly well understood. The complexity of regulated transcriptiona l expression of Alus is becoming apparent and insight into the mechani sm of retrotransposition is emerging. Unresolved questions concern why mobile, highly repetitive short interspersed elements (SINEs) have be en tolerated throughout evolution and why and how families of such seq uences are periodically replaced. Either certain SINEs are more succes sful genomic parasites or positive selection drives their relative suc cess and genomic maintenance. A complete understanding of the evolutio nary dynamics and significance of SINEs requires determining whether o r not they have a function(s), Recent evidence suggests two possibilit ies, one concerning DNA and the other RNA. Dispersed Alus exhibit rema rkable tissue-specific differences in the level of their 5-methylcytos ine content. Differences in Alu methylation in the male and female ger mlines suggest that Alu DNA may be involved in either the unique chrom atin organization of sperm or signaling events in the early embryo. Al u RNA is increased by cellular insults and stimulates protein synthesi s by inhibiting PKR, the eIF2 kinase that is regulated by double-stran ded RNA, PKR serves other roles potentially linking Alu RNA to a varie ty of vital cell functions. Since Alus have appeared only recently wit hin the primate lineage, this proposal provokes the challenging questi on of how Alu RNA could have possibly assumed a significant role in ce ll physiology.