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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

Human RNA methyltransferase BCDIN3D regulates microRNA processing

Blerta Xhemalce1, Samuel C Robson, Tony Kouzarides

  • 1Wellcome Trust/Cancer Research UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.

Cell
|October 16, 2012
PubMed

Insights

A novel RNA methyltransferase, BCDIN3D, was found to O-methylate microRNA (miRNA) precursors, inhibiting their maturation. This discovery reveals a new miRNA methylation pathway that impacts cancer cell growth.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cancer Research

Background:

  • MicroRNAs (miRNAs) are crucial regulators of biological processes, and their dysregulation is linked to cancer.
  • miRNA biogenesis involves sequential processing by Drosha and Dicer, generating 5' monophosphate ends essential for function.
  • Dicer's recognition of the 5' monophosphate of pre-miRNAs is critical for accurate miRNA production.

Purpose of the Study:

  • To identify novel regulators of miRNA biogenesis.
  • To investigate the role of RNA methyltransferases in miRNA processing.
  • To explore the potential involvement of miRNA regulation in cancer.

Main Methods:

  • In vitro and in vivo biochemical assays to study BCDIN3D activity.
  • Analysis of pre-miRNA and mature miRNA levels following BCDIN3D manipulation.
  • Assessment of breast cancer cell phenotypes upon BCDIN3D depletion.

Main Results:

  • BCDIN3D, a RNA-methyltransferase, was identified as an O-methylator of the 5' monophosphate of pre-miRNAs.
  • BCDIN3D was shown to phospho-dimethylate pre-miR-145, reducing its processing by Dicer.
  • Depletion of BCDIN3D in breast cancer cells increased mature miR-145 levels and suppressed tumorigenic phenotypes.

Conclusions:

  • BCDIN3D negatively regulates miRNA maturation through O-methylation of pre-miRNAs.
  • This novel miRNA methylation pathway antagonizes Dicer-dependent processing, impacting miR-145 and potentially other miRNAs.
  • The findings suggest a new mechanism of miRNA regulation relevant to cancer biology.

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