N6-methyl-adenosine (m6A) marks primary microRNAs for processing

N6-methyl-adenosine (m6A) marks primary microRNAs for processing

2015 March 26 | Claudio R. Alarcón, Hyeseung Lee*, Hani Goodarzi*, Nils Halberg, and Sohail F. Tavazoie
The study investigates the role of N6-methyladenosine (m6A) in the processing of primary microRNAs (pri-miRNAs). The authors found that METTL3, an RNA methyltransferase, methylates pri-miRNAs, marking them for recognition and processing by the microprocessor complex, which consists of the RNA binding protein DGCR8 and the ribonuclease DROSHA. METTL3 depletion reduced the binding of DGCR8 to pri-miRNAs, leading to a global reduction in mature miRNA levels and an accumulation of unprocessed pri-miRNAs. In vitro processing reactions confirmed that the m6A mark is essential for pri-miRNA processing. Gain-of-function experiments showed that METTL3 is sufficient to enhance miRNA maturation in a non-cell-type specific manner. These findings reveal that the m6A mark acts as a key post-transcriptional modification that initiates miRNA biogenesis.The study investigates the role of N6-methyladenosine (m6A) in the processing of primary microRNAs (pri-miRNAs). The authors found that METTL3, an RNA methyltransferase, methylates pri-miRNAs, marking them for recognition and processing by the microprocessor complex, which consists of the RNA binding protein DGCR8 and the ribonuclease DROSHA. METTL3 depletion reduced the binding of DGCR8 to pri-miRNAs, leading to a global reduction in mature miRNA levels and an accumulation of unprocessed pri-miRNAs. In vitro processing reactions confirmed that the m6A mark is essential for pri-miRNA processing. Gain-of-function experiments showed that METTL3 is sufficient to enhance miRNA maturation in a non-cell-type specific manner. These findings reveal that the m6A mark acts as a key post-transcriptional modification that initiates miRNA biogenesis.
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[slides and audio] N6-methyladenosine marks primary microRNAs for processing