Methylation by NSun2 represses the levels and function of microRNA 125b

Area of Science:

• Molecular Biology
• RNA Biology
• Epigenetics

Background:

• Methylation is a key posttranscriptional RNA modification.
• The methylation status of mammalian microRNAs was previously unknown.

Purpose of the Study:

• To investigate whether mammalian microRNAs are subject to methylation.
• To identify the enzyme responsible for microRNA methylation and its functional consequences.

Main Methods:

• In vitro and in vivo experiments were conducted.
• The tRNA methyltransferase NSun2 was examined for its role in microRNA methylation.
• The impact of methylation on microRNA processing and function was assessed.

Main Results:

• NSun2 was found to methylate primary (pri-miR-125b), precursor (pre-miR-125b), and mature microRNA 125b (miR-125b).
• NSun2-mediated methylation inhibits pri-miR-125b processing and pre-miR-125b cleavage.
• Methylation attenuates RISC recruitment by miR-125b, repressing gene silencing function.

Conclusions:

• NSun2 methylates miR-125b, impacting its maturation and function.
• RNA methylation represents a novel regulatory mechanism for microRNA activity.
• This finding sheds light on the regulation of gene expression by microRNAs.