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Updated: Jan 9, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

8.9K

Domain associated with zinc fingers-containing NF90-NF45 complex inhibits m6A modification of primary microRNA by

Takuma Higuchi1, Shunsuke Morioka1, Keiko Morisawa1

  • 1Laboratory of Molecular Biology, Science Research Center, Kochi Medical School, Kochi University, Japan.

FEBS Open Bio
|December 6, 2025
PubMed

Insights

NF90-NF45 negatively regulates N6-methyladenosine (m6A) modification of primary microRNAs (pri-miRNAs) by methyltransferase-like 3/14 (METTL3/14). NF90-NF45 competes with METTL3/14 for pri-miRNA binding, impacting microRNA biogenesis.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • RNA Biology

Background:

  • N6-methyladenosine (m6A) modification is crucial for microRNA (miRNA) biogenesis.
  • The precise regulatory mechanisms governing m6A modification of primary miRNAs (pri-miRNAs) are not fully understood.

Purpose of the Study:

  • To elucidate the regulatory mechanism of m6A modification in pri-miRNA processing.
  • To identify factors that modulate the interaction between m6A machinery and pri-miRNAs.

Main Methods:

  • Overexpression constructs were used to study the effects of METTL3/14 and NF90-NF45 on miRNA biogenesis.
  • In vitro assays assessed the impact of NF90-NF45 on m6A modification of specific pri-miRNAs.
  • Immunoprecipitation analysis was performed to investigate protein-protein interactions.

Main Results:

  • NF90-NF45 acts as a negative regulator of pri-miRNA m6A modification by METTL3/14.
  • NF90-NF45 suppressed miR-7 biogenesis, while METTL3/14 promoted it; METTL3/14 overexpression counteracted NF90-NF45's inhibitory effect.
  • NF90-NF45 specifically inhibited m6A modification of pri-mir-7-1 but not pri-mir-200a due to differential binding affinity.
  • NF90-NF45 does not directly interact with METTL3/14.

Conclusions:

  • NF90-NF45 negatively regulates METTL3/14-mediated m6A modification of pri-miRNAs.
  • The regulation occurs through NF90-NF45 competing with METTL3/14 for binding to pri-miRNAs.
  • This competition mechanism influences miRNA biogenesis and provides insight into post-transcriptional gene regulation.
Keywords:
RNA binding proteinRNA metabolismRNA methylationRNA methyltransferaseRNA modificationmiRNA biogenesis

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