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Analysis of Termination of Transcription Using BrUTP-strand-specific Transcription Run-on TRO Approach
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Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs

Ashish Dhir1, Somdutta Dhir1, Nick J Proudfoot1

  • 1Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

Nature Structural & Molecular Biology
|March 3, 2015
PubMed

Insights

Most long noncoding RNAs containing microRNAs (miRNAs) are terminated by Microprocessor cleavage, not polyadenylation. This RNase III-mediated process prevents transcriptional readthrough and interference with other genes.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • RNA Processing

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression at the post-transcriptional level.
  • Mammalian miRNA biogenesis involves the Microprocessor complex for cotranscriptional cleavage of RNA polymerase II (Pol II) transcripts.
  • While many miRNAs are intronic, a significant portion originates from long noncoding RNAs (lncRNAs), with poorly understood processing mechanisms.

Purpose of the Study:

  • To investigate the transcript processing and termination mechanisms of lncRNAs containing miRNAs (lnc-pri-miRNAs).
  • To determine if lnc-pri-miRNAs utilize the canonical cleavage-and-polyadenylation pathway for termination.
  • To elucidate the role of the Microprocessor complex in lnc-pri-miRNA processing and its impact on gene expression.

Main Methods:

  • Detailed characterization of the liver-specific lnc-pri-miR-122 transcript.
  • Genome-wide analysis of lnc-pri-miRNA processing in human cell lines.
  • Assessment of Microprocessor complex activity and its effect on transcription termination.

Main Results:

  • Most lnc-pri-miRNAs are not terminated by the canonical cleavage-and-polyadenylation pathway.
  • Microprocessor cleavage serves as the primary termination mechanism for lnc-pri-miRNAs.
  • Inactivation of the Microprocessor complex results in extensive transcriptional readthrough of lnc-pri-miRNAs.
  • Transcriptional readthrough interferes with the expression of downstream genes.

Conclusions:

  • A novel RNase III-mediated, polyadenylation-independent mechanism for Pol II transcription termination in mammalian cells is defined.
  • Microprocessor-dependent termination is crucial for preventing transcriptional interference from lnc-pri-miRNAs.
  • This finding reveals a new layer of gene regulation involving lncRNA processing and transcription termination.

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