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Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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Published on: June 15, 2016

Nuclear factor TDP-43 can affect selected microRNA levels.

Emanuele Buratti1, Laura De Conti, Cristiana Stuani

  • 1International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.

The FEBS Journal
|April 29, 2010
PubMed
Summary

TDP-43 protein impacts microRNA (miRNA) synthesis. Knockdown of TDP-43 altered expression of specific miRNAs, let-7b and miR-663, which directly bind to TDP-43, affecting gene expression.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • TDP-43 is a key component of inclusions in neurodegenerative diseases like ALS and FTLD.
  • TDP-43 has known roles in transcription, splicing, and mRNA stability.
  • Its precise function in microRNA (miRNA) synthesis remains largely unexplored.

Purpose of the Study:

  • To investigate the impact of TDP-43 on the overall miRNA population in cultured cells.
  • To identify specific miRNAs whose expression is modulated by TDP-43 levels.

Main Methods:

  • TDP-43 knockdown in cultured cells.
  • Microarray analysis to assess global miRNA expression changes.
  • Real-time PCR for validation of specific miRNA expression.
  • RNA-binding assays to confirm direct miRNA-TDP-43 interactions.

Main Results:

  • TDP-43 knockdown led to significant changes in miRNA expression profiles.
  • Specifically, let-7b expression decreased, while miR-663 expression increased.
  • Direct binding of let-7b (within the miRNA) and miR-663 (precursor hairpin) to TDP-43 was demonstrated.
  • Candidate target transcripts affected by these interactions were identified.

Conclusions:

  • TDP-43 plays a regulatory role in miRNA synthesis and expression.
  • Specific miRNAs, let-7b and miR-663, are direct binding partners of TDP-43.
  • These interactions influence gene expression, potentially contributing to TDP-43's role in neurodegeneration.