Long noncoding RNAs: Re-writing dogmas of RNA processing and stability

Area of Science:

• Molecular Biology
• Genomics
• RNA Biology

Background:

• The human genome produces a vast array of transcripts, including numerous long noncoding RNAs (lncRNAs).
• While many lncRNAs possess canonical 5' cap and poly(A) tail structures, some abundant lncRNAs exhibit non-canonical processing and lack these features.
• Understanding the generation, stabilization, and function of these non-canonical lncRNAs is crucial for comprehending gene regulation.

Purpose of the Study:

• To highlight the unique mechanisms governing the generation, stabilization, and function of specific abundant, non-canonical long noncoding RNAs.
• To explore how these lncRNAs achieve stability and carry out their roles without canonical 5' cap and poly(A) tail structures.
• To underscore the emerging understanding of diverse post-transcriptional control mechanisms for lncRNAs.

Main Methods:

• Review and synthesis of existing literature on well-characterized non-canonical lncRNAs.
• Focus on specific examples such as MALAT1, MEN β (NEAT1_2), sno-lncRNAs, and circular RNAs.
• Analysis of the structural and mechanistic basis for the stability and function of these RNAs.

Main Results:

• MALAT1 and MEN β (NEAT1_2) are highly abundant nuclear lncRNAs involved in cancer progression and paraspeckle formation, respectively.
• These lncRNAs are not polyadenylated; their 3' ends are processed by tRNA biogenesis machinery and stabilized by conserved triple helical structures.
• Sno-lncRNAs lack poly(A) tails and feature snoRNA structures at their termini, while circular RNAs generated by splicing are resistant to exonucleases.

Conclusions:

• Abundant long noncoding RNAs employ diverse, non-canonical strategies for stability and function, diverging from canonical mRNA processing.
• Mechanisms include tRNA-derived 3' end processing, triple helical structures, snoRNA integration, and circularization, all contributing to stability.
• These findings suggest that unique post-transcriptional control mechanisms are common for regulating long noncoding RNA activity.