Inverted repeat Alu elements in the human lincRNA-p21 adopt a conserved secondary structure that regulates RNA function

LincRNA-p21 is a long intergenic non-coding RNA (lincRNA) involved in the p53-mediated stress response. Yale University researchers sequenced the human lincRNA-p21 (hLincRNA-p21) and found that it has a single exon that includes inverted repeat Alu elements (IRAlus). Sense and antisense Alu elements fold independently of one another into a secondary structure that is conserved in lincRNA-p21 among primates. Moreover, the structures formed by IRAlus are involved in the localization of hLincRNA-p21 in the nucleus, where hLincRNA-p21 colocalizes with paraspeckles. These results underscore the importance of IRAlus structures for the function of hLincRNA-p21 during the stress response.

Inverted repeat Alu elements (IRAlus) in hLincRNA-21
fold as independent structural domains in vitro

(A and B) Experimentally-derived secondary structures of sense (C) and antisense (D) Alu sequences of hLincRNA-p21. A schematic diagram of hLincRNA-p21 LIsoE2 isoform highlights the relative position of each structure in the RNA sequence (top). Colors of the circles around each nucleotide indicate SHAPE reactivity. The dotted lines represent putative tertiary contacts between the terminal loops of the three-way junctions. Data values are the mean of two biological replicates. Observed U to C transitions are indicated by colored arrowheads. The frequency values represent the fraction of observed transitions of n = 93 sequences from eight biological replicates for the sense Alu and n = 35 sequences from three biological replicates for the antisense Alu. Covariation of lincRNA-p21 in human and nine other primates is shown in boxes for selected regions.