TDP-43 regulates transcription at protein-coding genes and Alu retrotransposons
AffiliationUniv Arizona, Dept Mol & Cellular Biol
Univ Arizona, Dept Chem & Biochem
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CitationMorera, A. A., Ahmed, N. S., & Schwartz, J. C. (2019). TDP-43 regulates transcription at protein-coding genes and Alu retrotransposons. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms, 1862(10), 194434.
Rights© 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
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AbstractThe 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.
NoteOpen access article
VersionFinal published version
SponsorsNational Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NS082376]; Office of the Director, National Institutes of Health of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [S10OD013237]