Structural Modifications and Novel Protein-Binding Sites in Pre-miR-675—Explaining Its Regulatory Mechanism in Carcinogenesis

Abstract

Pre-miR-675 is a microRNA expressed from the exon 1 of H19 long noncoding RNA, and the atypical expression of pre-miR-675 has been linked with several diseases and disorders including cancer. To execute its function inside the cell, pre-miR-675 is folded into a particular conformation, which aids in its interaction with several other biological molecules. However, the exact folding dynamics of pre-miR-675 and its protein-binding motifs are currently unknown. Moreover, how H19 lncRNA and pre-miR-675 crosstalk and modulate each other’s activities is also unclear. The detailed structural analysis of pre-miR-675 in this study determines its earlier unknown conformation and identifies novel protein-binding sites on pre-miR-675, thus making it an excellent therapeutic target against cancer. Co-folding analysis between H19 lncRNA and pre-miR-675 determine structural transformations in pre-miR-675, thus describing the earlier unknown mechanism of interaction between these two molecules. Comprehensively, this study details the conformation of pre-miR-675 and its protein-binding sites and explains its relationship with H19 lncRNA, which can be interpreted to understand the role of pre-miR-675 in the development and progression of tumorigenesis and designing new therapeutics against cancers.

Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: Implications to alternative conformations and their statistical structural analyses

“…Following chemical probing, both modified and un-modified RNA were reverse transcribed using specific primer complementary to the 3’ RNA cassette (Dey 2023) and Superscript II reverse transcriptase under error prone conditions as previously described (Smola et al 2015). The generated cDNA was purified using G50 column (GE healthcare) and subjected to second strand synthesis (NEBNext Second Strand Synthesis Module).…”

Molecular Mechanisms and Clinical Implications of Noncoding RNAs in Cancer

“…Multiple other direct and indirect targets that exert miR-4646-5p tumor-suppressive effects, such as the cytokines and chemokines GCSF and IL6, which have tumor-promoting functions, were also explored, providing a theoretical basis for the combined treatment of TNBC with miR-4646-5p and immunotherapy, such as checkpoint inhibitors. PremiR-675 is a miRNA expressed by H19 lncRNA, and its abnormal expression is associated with various diseases, such as cancer and cardiovascular and neurological disorders [ 16 ]. Furthermore, Dey’s research revealed that premiR-675 could fold into a typical stem–loop helical conformation and has binding sites for FUS, SRSF1, SRSF9, FXR2, LIN28B, and HUR proteins, which can be further used for structure-based drug design.…”