From 'JUNK' to just unexplored noncoding knowledge: the case of transcribed Alus

Abstract

Non-coding RNAs (ncRNAs) are increasingly being implicated in diverse functional roles. Majority of these ncRNAs have their origin in the repetitive elements of genome. Significantly, increase in genomic complexity has been correlated with increase in repetitive content of the genome. Primate-specific Alu repeats, belonging to SINE class of repeats, is the most abundant repeat class inhabiting the human genome. Of the many possible functional roles of Alu repeats, they have been shown to modulate human transcriptome by virtue of harboring diverse array of functional RNA pol II TFBS, cryptic splice-site-mediated Alu exonization and as probable miRNA targets. Retro-transposition of Alu harboring TFBS has shaped up gene-specific regulatory networks. Alu exonized transcripts are raw material for dsRNA-mediated A-I editing leading to nuclear retention of transcripts and change in miRNA target. miRNA targets within Alu may titrate the effective miRNA or transcript concentration, thus acting as 'miRNA sponge'. Differential levels of Alu RNA during different conditions of stress also await clear functional understanding. These have contributed toward evolution of complex regulatory repertoire leading to the evolution of primate-specific functions. Recent reports of co-localization of pol II and pol III binding sites near the gene and elsewhere in the genome, increase the possibility of dynamic co-ordination between both pol II and pol III determining the ultimate transcriptional outcome. Dynamic and functional Alu repeats seem to be centrally placed to modulate the transcriptional landscape of human genome.