RNA 2'-O-Methylation (Nm) Modification in Human Diseases

Abstract

Nm (2'-O-methylation) is one of the most common modifications in the RNA world. It has the potential to influence the RNA molecules in multiple ways, such as structure, stability, and interactions, and to play a role in various cellular processes from epigenetic gene regulation, through translation to self versus non-self recognition. Yet, building scientific knowledge on the Nm matter has been hampered for a long time by the challenges in detecting and mapping this modification. Today, with the latest advancements in the area, more and more Nm sites are discovered on RNAs (tRNA, rRNA, mRNA, and small non-coding RNA) and linked to normal or pathological conditions. This review aims to synthesize the Nm-associated human diseases known to date and to tackle potential indirect links to some other biological defects.

Keywords: 2′-O-methylation (Nm); RNA modifications; epitranscriptomics; human diseases.

Figure 1

2′-O-methylated ribonucleoside (Nm): A –CH₃ group is replacing the –H at the position 2′ in the ribose moiety. This modification can appear on any nucleotide regardless of the type of nitrogenous base (Base).

Figure 2

Representation of the mature human tRNA^Phe (76 nucleotides). The two Nm modifications in the anticodon loop, in C₃₂ and G₃₄, are placed by the 2′-O-methyltransferase FTSJ1 and are annotated in red. Blue circles are for non-modified nucleotides, black circles mean modified nucleotides (adapted from http://modomics.genesilico.pl/).

Figure 3

RNA cap structure: The cap0 structure consists of a guanosine residue, methylated in the N-7 position, which is bound to the terminal 5′-end nucleotide of the mRNA with a 5′-5′ triphosphate bridge. Subsequent 2′-O-methylation in the ribose of the first, or both the first and the second, transcribed mRNA nucleotides leads to the formation of cap1 or cap2, respectively. This figure has been adapted from Reference [151].