Structural conservation of MALAT1 long-non-coding RNA in vivo and in evolution

The long non-coding RNA (lncRNA) Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is derived by RNase P cleavage of mascRNA, a small tRNA-like non-coding RNA. Although not canonically poly adenylated MALAT1 is stabilized by a highly conserved 159 nucleotide triple helix structure on its 3' end. The entire MALAT1 transcript is over 8kb in humans and is considered one of the most conserved lncRNAs at the sequence and structure level. Nonetheless, the strongest structural conservation signal (as measured by co-variation of base-pairs) is in the triple helix structure. As a result, primary sequence analysis of co-variation cannot alone confirm the degree of structural conservation of the entire transcript. Furthermore, RNA structure is often context dependent; RNA binding proteins differentially expressed in different cell types may alter structure. We investigate here the in and ex vivo structure of the full-length human and green monkey (Chlorocebus sabaeus) MALAT1 transcript in multiple, tissue derived cell lines using SHAPE chemical probing. Our data reveals surprising levels of uniform structural conservation in different cell lines, in versus ex vivo and even between these species despite significant genetic differences. The uniformity of the structural conservation across the entire transcript suggests that despite seeing co-variation signals only in the three-helix junction of the lncRNA, the rest of the transcript's structure is remarkably robust at least in primates across multiple tissue types.