Sequence and phylogenetic analysis revealed structurally conserved domains and motifs in lincRNA-p21

Abstract

Long Intergenic Non-coding RNAs (lincRNAs) are the largest class of long non-coding RNAs in the eukaryotes, which originate from the intergenic regions of the genome. A ~4kb long lincRNA-p21 is derived from a transcription unit next to the p21/Cdkn1a gene locus. LincRNA-p21 plays key regulatory roles in p53 dependent transcriptional repression and translational repression through its physical association with proteins such as hnRNP-K and HuR.It is also involved in the aberrant gene expression in different cancers. However, detailed information on its structure, recognition, and trans-regulation by proteins is not well known. In this study, we have carried out a complete gene analysis and annotation of lincRNA-p21. This analysis showed that lincRNA-p21 is highly conserved in primates, and its conservation drops significantly in lower organisms. Furthermore, our analysis has revealed two structurally conserved domains in the 5 and 3 terminal regions of lincRNA-p21. Phylogenetic analysis has revealed discrete evolutionary dynamics in these conserved domains for orthologous sequences of lincRNA-p21, which have evolved slowly across primates compared to other mammals. Using Infernal based covariance analysis, we have computed the secondary structures of these domains. The secondary structures were further validated by energy minimization criteria for individual orthologous sequences as well as the full-length human lincRNA-p21. In summary, this analysis has led to the identification of sequence and structural motifs in the conserved fragments, indicating the functional importance for these regions.