Pre-miR-675的结构修饰和新型蛋白结合位点--解释其在致癌过程中的调控机制

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Non-Coding RNA Pub Date : 2023-08-10 DOI:10.3390/ncrna9040045
Abhishek Dey
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引用次数: 0

摘要

pre-miR-675 是一种从 H19 长非编码 RNA 第 1 外显子表达的 microRNA,pre-miR-675 的非典型表达与包括癌症在内的多种疾病和失调有关。为了在细胞内执行其功能,pre-miR-675 折叠成一个特定的构象,这有助于它与其他几种生物分子的相互作用。然而,pre-miR-675 的确切折叠动态及其蛋白质结合基团目前尚不清楚。此外,H19 lncRNA 和 pre-miR-675 如何相互影响和调节彼此的活性也不清楚。本研究对pre-miR-675进行了详细的结构分析,确定了其早期未知的构象,并发现了pre-miR-675上新的蛋白结合位点,从而使其成为癌症的一个极佳治疗靶点。H19 lncRNA与pre-miR-675之间的共折叠分析确定了pre-miR-675的结构转变,从而描述了这两个分子之间早先未知的相互作用机制。总之,本研究详细阐述了pre-miR-675的构象及其蛋白结合位点,并解释了其与H19 lncRNA的关系,可用于理解pre-miR-675在肿瘤发生和发展过程中的作用,并设计新的抗癌疗法。
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Structural Modifications and Novel Protein-Binding Sites in Pre-miR-675-Explaining Its Regulatory Mechanism in Carcinogenesis.

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.

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来源期刊
Non-Coding RNA
Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
6.70
自引率
4.70%
发文量
74
审稿时长
10 weeks
期刊介绍: Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.
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