Beyond reader proteins: RNA binding proteins and RNA modifications in conversation to regulate gene expression

Area of Science:

• Molecular Biology
• Biochemistry
• Genetics

Background:

• Post-transcriptional mRNA modifications critically influence gene expression and RNA function.
• RNA modifications can alter interactions between RNA and RNA-binding proteins (RBPs).
• While some modifications like m6A have known readers, many RBP-RNA modification interactions remain poorly understood.

Purpose of the Study:

• To review known instances where RNA modifications affect RBP binding.
• To examine the biochemical properties of various mRNA modifications and their likely impact on RNA:RBP interactions.
• To discuss strategies for identifying novel modification-sensitive RBP:RNA interactions.

Main Methods:

• Literature review of studies on RNA modifications (m6A, m1A, m5C, Ψ, N7-methylguanosine, D, ac4C, Nme) and their effects on RBP binding.
• Analysis of biochemical properties of modifications, including hydrogen bonding, base-stacking, and conformational preferences.
• Discussion of RNA secondary structure changes induced by modifications and their influence on protein binding.

Main Results:

• Specific mRNA modifications, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), pseudouridine (Ψ), and N7-methylguanosine, are known to alter RBP binding.
• Biochemical properties such as altered hydrogen bond potential, base-stacking efficiency, and RNA conformational preferences are key mechanisms.
• RNA modifications can indirectly affect protein binding through changes in RNA secondary structure.

Conclusions:

• Understanding how RNA modifications influence RBP binding is crucial for deciphering gene expression regulation.
• Future research should focus on identifying new modification-sensitive RBP:RNA interactions.
• Integrating epitranscriptomic and RNA-protein interactome data will elucidate recognition rules and biological consequences of mRNA modifications.