Potential G-Quadruplex Forming Sequences and N⁶-Methyladenosine Colocalize at Human Pre-mRNA Intron Splice Sites

Area of Science:

• Molecular Biology
• Genomics
• Biochemistry

Background:

• mRNA maturation involves crucial epitranscriptomic modifications.
• Site selection for these modifications suggests a role for RNA secondary structures.
• RNA G-quadruplexes (rG4s) are noncanonical structures with potential regulatory functions.

Purpose of the Study:

• To investigate the colocalization of potential RNA G-quadruplex (rG4) sequences with major epitranscriptomic modifications in human mRNA and pre-mRNA.
• To explore the potential functional implications of this colocalization in mRNA biogenesis and regulation.

Main Methods:

• Bioinformatic analysis of published human mRNA and pre-mRNA datasets.
• Identification and localization of potential rG4 sequences.
• Correlation analysis with known epitranscriptomic modification sites (m6A, Ψ, I).

Main Results:

• Potential rG4 sequences colocalize with N6-methyladenosine (m6A), pseudouridine (Ψ), and inosine (I) in human mature mRNA.
• Colocalization of potential rG4s and m6A is most prominent in pre-mRNA introns near splice sites, with specific sequence motifs.
• rG4s also show colocalization with Ψ and I sites in mRNA, though less frequently than with m6A.

Conclusions:

• Potential rG4s and m6A may collaborate in regulating alternative splicing of pre-mRNA.
• The interplay between rG4 structures and epitranscriptomic modifications could influence cellular phenotype.
• Further experimental validation is needed to elucidate the functional mechanisms of this collaboration.