Understanding the Functions of Long Non-Coding RNAs through Their Higher-Order Structures

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Thousands of long non-coding RNAs (lncRNAs) exist, but their functions remain largely unknown due to poor structural understanding.
• Elucidating lncRNA structure is crucial for understanding their regulatory roles in biological processes.

Purpose of the Study:

• To review structure-function relationships of prominent lncRNAs in animals and plants.
• To highlight in vitro and in vivo technologies for lncRNA structure determination.
• To bridge the gap between lncRNA structure and biological function.

Main Methods:

• Review of existing literature on lncRNA structure and function.
• Focus on structure probing techniques: dimethyl sulfate-sequencing (DMS-seq), selective 2'-hydroxyl acylation analyzed by primer extension-sequencing (SHAPE-seq), parallel analysis of RNA structure (PARS), and fragmentation sequencing (FragSeq).

Main Results:

• lncRNA structure determination is challenging due to their high molecular weight and difficulty in crystallization.
• Various sequencing-based methods (DMS-seq, SHAPE-seq, PARS, FragSeq) offer powerful tools for in vitro and in vivo RNA structure analysis.
• Structure-function relationships are being uncovered for key lncRNAs across kingdoms.

Conclusions:

• A deeper understanding of lncRNA structure is essential for deciphering their complex biological functions.
• Advanced structural analysis technologies are critical for future lncRNA research.
• This review provides a foundation for studying lncRNA mechanisms at the structural level.