Noncanonical metabolite RNA caps: Classification, quantification, (de)capping, and function

Area of Science:

• Molecular Biology
• RNA Biology
• Biochemistry

Background:

• The 5' cap of eukaryotic mRNA is crucial for mRNA stability and translation.
• Recent discoveries reveal novel 5'-terminal RNA caps derived from cellular metabolites in both eukaryotes and prokaryotes.
• These noncanonical caps, resembling the 7-methylguanosine (m7G) structure, originate from molecules like NAD, FAD, CoA, and dinucleoside polyphosphates (NpnN).

Purpose of the Study:

• To investigate the significance and characteristics of noncanonical RNA caps.
• To compare the prevalence, quantity, and features of metabolite-capped RNAs.
• To understand the biological impact and regulatory role of these novel RNA caps.

Main Methods:

• Structured analysis of existing studies.
• Integration of functional, quantitative, and sequencing data.
• Examination of biosynthetic pathways and decapping machinery.

Main Results:

• Noncanonical caps differ across transcripts and RNA types, varying with environmental stimuli.
• Analysis reveals distinct classes of metabolite-capped RNAs.
• Biosynthetic and decapping mechanisms highlight the regulation and turnover of these RNAs.

Conclusions:

• Noncanonical capping is a universal and ancient RNA modification.
• Organisms have evolved diverse strategies to utilize metabolite-derived caps.
• Metabolite-capped RNAs introduce an additional layer of RNA regulation.