InvAluable junk: the cellular impact and function of Alu and B2 RNAs

Abstract

The short interspersed elements (SINEs) Alu and B2 are retrotransposons that litter the human and mouse genomes, respectively. Given their abundance, the manner in which these elements impact the host genome and what their biological functions might be is of significant interest. Finding that Alu and B2 SINEs are transcribed, both as distinct RNA polymerase III transcripts and as part of RNA polymerase II transcripts, and that these SINE encoded RNAs indeed have biological functions has refuted the historical notion that SINEs are merely "junk DNA." This article reviews currently known cellular functions of both RNA polymerase II and RNA polymerase III transcribed Alu and B2 RNAs. These RNAs, in different forms, control gene expression by participating in processes as diverse as mRNA transcriptional control, A-to-I editing, nuclear retention, and alternative splicing. Future studies will likely reveal additional contributions of Alu and B2 RNAs as regulators of gene expression.

Figure 1

Upon heat shock, Pol III transcription of B1 and B2 RNAs in mouse cells and Alu RNA in human cells increases. B2 or Alu RNA can inhibit Pol II mRNA synthesis by entering complexes at the promoters of repressed genes.

Figure 2

Two nearby Alu sequences in an inverted orientation can form a “fold-back” structure in the 3’-UTR of a mRNA. This long stretch of dsRNA is an ideal substrate for adenosine deamination by the ADAR enzymes. The highly edited Alu RNA duplex is then bound by the RNA binding protein p54^nrb and the mRNA is retained in the nucleus, thereby preventing translation.

Figure 3

Embedded Alu RNAs can be alternatively spliced. A) Schematic of the potential splice sites in the sense and antisense Alu sequence (62). Arrows above the Alu elements indicate potential 5’ splice sites, arrows below the Alu elements indicate potential 3’ splice sites. B) Schematic illustrating exonization of an embedded antisense Alu RNA. Sequences within Alu RNA are recognized as splice sites, resulting in a mature mRNA isoform containing a portion of the Alu sequence.