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

Abstract

Although not canonically polyadenylated, the long non-coding RNA MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is stabilized by a highly conserved 159 nucleotide triple helix structure on its 3 end. The entire MALAT1 transcript is over 8,000 nucleotides long in humans and is considered one of the most conserved lncRNAs, at both the sequence and structure levels. The strongest structural conservation signal (as measured by co-variation of base-pairs) is in the triple helix structure. Primary sequence analysis of co-variation alone cannot confirm the degree of structural conservation of the entire full-length transcript. Furthermore, RNA structure is often context dependent; RNA binding proteins that are differentially expressed in different cell types may alter structure. We investigate here the in cell and cell free structures of the full-length human and green monkey (Chlorocebus sabaeus) MALAT1 transcripts in multiple tissue-derived cell lines using SHAPE chemical probing. Our data reveals surprising levels of uniform structural conservation in different cell lines, in cells and cell free, and even between species, despite significant differences in primary sequence. 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 transcripts structure is remarkably conserved at least in primates and across multiple cell types and conditions.