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Use of Alu Element Containing Minigenes to Analyze Circular RNAs
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The human MAPT locus generates circular RNAs.

Justin R Welden1, Jacob van Doorn1, Peter T Nelson1

  • 1University of Kentucky, Lexington, KY 40503, United States.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|May 6, 2018
PubMed
Summary
This summary is machine-generated.

Researchers discovered novel circular RNAs from the MAPT gene in human brains. These circular RNAs may regulate Tau protein and contribute to tauopathies like Alzheimer's disease.

Keywords:
Alternative pre-mRNA splicingAlzheimer's diseaseCircular RNAsGene expressionTau

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • The microtubule-associated protein Tau (MAPT) is implicated in neurodegenerative tauopathies, including Alzheimer's disease (AD) and frontotemporal dementia (FTD).
  • Aberrant pre-mRNA splicing of the MAPT gene is linked to FTD, highlighting the importance of MAPT RNA regulation.

Purpose of the Study:

  • To identify novel RNA species generated from the MAPT locus in human brain tissue.
  • To investigate the potential role of these novel RNAs in Tau regulation and tauopathies.

Main Methods:

  • Utilized PCR screening of RNA from human brain tissues to detect circular RNAs.
  • Employed transfection of HEK293 cells to study the regulation of MAPT circular RNAs by specific proteins.

Main Results:

  • Identified bona fide circular RNAs produced from the MAPT locus via backsplicing (exon 12 to exon 10 or 7).
  • These MAPT circular RNAs are cytosolic and contain open reading frames encoding Tau protein fragments.
  • Regulatory proteins (CLK2, SRSF7/9G8, PP1, NIPP1) were found to reduce the abundance of MAPT exon 12→10 backsplice RNA.

Conclusions:

  • Reported the identification of new MAPT circular RNAs in the human brain.
  • These circular RNAs may be involved in normal Tau regulation.
  • The potential to encode Tau fragments with multiple microtubule-binding sites suggests a role in the pathogenesis of tauopathies.