Contribution of structural accessibility to the cooperative relationship of TF-lncRNA in myopia.

Abstract

Transcriptional regulation is associated with complicated mechanisms including multiple molecular interactions and collaborative drive. Long noncoding RNAs (lncRNAs) have highly structured characteristics and play vital roles in the regulation of transcription in organisms. However, the specific contributions of conformation feature and underlying molecular mechanisms are still unclear. In the present paper, a hypothesis regarding molecular structure effect is presented, which proposes that lncRNAs fold into a complex spatial architecture and act as a skeleton to recruit transcription factors (TF) targeted binding, and which is involved in cooperative regulation. A candidate set of TF-lncRNA coregulation was constructed, and it was found that structural accessibility affected molecular binding force. In addition, transcription factor binding site (TFBS) regions of myopia-related lncRNA transcripts were disturbed, and it was discovered that base mutations affected the occurrence of significant molecular allosteric changes in important elements and variable splicing regions, mediating the onset and development of myopia. The results originated from structureomics and interactionomics and created conditions for systematic research on the mechanisms of structure-mediated TF-lncRNA coregulation in transcriptional regulation. Finally, these findings will help further the understanding of key regulatory roles of molecular allostery in cell physiological and pathological processes.