Detection of Allosteric Effects of lncRNA Secondary Structures Altered by SNPs in Human Diseases

Abstract

Recent studies have shown that structuralized long non-coding RNAs (lncRNAs) play important roles in genetic and epigenetic processes. The spatial structures of most lncRNAs can be altered by distinct in vivo and in vitro cellular environments, as well as by DNA structural variations, such as single-nucleotide polymorphisms (SNPs) and variants (SNVs). In the present study, we extended candidate SNPs that had linkage disequilibria with those significantly associated with lung diseases in genome-wide association studies in order to investigate potential disease mechanisms originating from SNP structural changes of host lncRNAs. Following accurate alignments, we recognized 115 ternary-relationship pairs among 41 SNPs, 10 lncRNA transcripts, and 1 type of lung disease (adenocarcinoma of the lung). Then, we evaluated the structural heterogeneity induced by SNP alleles by developing a local-RNA-structure alignment algorithm and employing randomized strategies to determine the significance of structural variation. We identified four ternary-relationship pairs that were significantly associated with SNPinduced lncRNA allosteric effects. Moreover, these conformational changes disrupted the interactive regions and binding affinities of lncRNA-HCG23 and TF-E2F6, suggesting that these may represent regulatory mechanisms in lung diseases. Taken together, our findings support that SNP-induced changes in lncRNA conformations regulate many biological processes, providing novel insight into the role of the lncRNA "structurome" in human diseases.

Association of BAFF/BAFF-R Single Nuclear Polymorphisms with Renal Graft Function in Kidney Transplant Recipients

“…Remarkable strides in SNP research have taken place since the construction of an SNP database [29], completion of protocols for a genome-wide, preponderant SNP network [30], and development of a model to predict tacrolimus levels in pediatric solid organ transplant recipients, by integrating clinical data with genetic factors [31]. The effect of the interaction between different SNPs, and between SNPs and non-coding RNAs (such as miRNA and lncRNA) on the translation, expression, and function of relevant genes forms an important component of SNP research [32,33].…”

LncRNA NEAT1 in the pathogenesis of liver‐related diseases

“…91 Transcription, posttranscriptional control, epigenetic regulation, and other physiological and pathological processes are all impacted by lncRNAs. 92 NEAT1 holds significant prominence among the lncRNAs in its contribution to the development of ALF. Regarding this, Wang et al…”

“…ALF is an uncommon yet perilous hepatic condition characterized by the sudden emergence of clinical morbidity and a significant risk of mortality 91 . Transcription, posttranscriptional control, epigenetic regulation, and other physiological and pathological processes are all impacted by lncRNAs 92 . NEAT1 holds significant prominence among the lncRNAs in its contribution to the development of ALF.…”