TDP-43 regulates transcription at protein-coding genes and Alu retrotransposons

Andrés A. Morera, Nasiha S. Ahmed, Jacob C. Schwartz

Research output: Contribution to journalArticle

Abstract

The 43-kDa transactive response DNA-binding protein (TDP-43) is an example of an RNA-binding protein that regulates RNA metabolism at multiple levels from transcription and splicing to translation. Its role in post-transcriptional RNA processing has been a primary focus of recent research, but its role in regulating transcription has been studied for only a few human genes. We characterized the effects of TDP-43 on transcription genome-wide and found that TDP-43 broadly affects transcription of protein-coding and noncoding RNA genes. Among protein-coding genes, the effects of TDP-43 were greatest for genes <30 thousand base pairs in length. Surprisingly, we found that the loss of TDP-43 resulted in increased evidence for transcription activity near repetitive Alu elements found within expressed genes. The highest densities of affected Alu elements were found in the shorter genes, whose transcription was most affected by TDP-43. Thus, in addition to its role in post-transcriptional RNA processing, TDP-43 plays a critical role in maintaining the transcriptional stability of protein-coding genes and transposable DNA elements.

Original languageEnglish (US)
Article number194434
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1862
Issue number10
DOIs
Publication statusPublished - Oct 2019

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Keywords

  • Alu SINE
  • GRO-seq
  • Retrotransposon
  • TARDBP
  • TDP-43
  • Transcription

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics

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