Reciprocal Regulation of Transcription for Protein-Coding and Non-Coding Alu Transcripts by TDP-43
AuthorMorera, Andrés Alejandro
AdvisorSchwartz, Jacob C.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractTAR DNA binding protein of 43 kDa (TDP-43) is a ubiquitously expressed RNA and DNA binding protein with reported functions in transcription, processing, transport, and translation of RNA transcripts. A vast majority of studies of TDP-43 pertain to its involvement in RNA splicing and RNA processing following transcription. However, to date, only a handful of studies have explored TDP-43’s role as a regulator of transcription. The present study for the first time characterizes the effects of TDP-43 depletion on transcription genome-wide in human cells. We employ global nuclear run-on sequencing (GRO-Seq) to identify sites of active transcription throughout the genome and change of transcription at these sites following depletion of TDP-43. We compare these GRO-Seq results to publicly available data from other genome-wide sequencing experiments to determine the contribution of TDP-43-dependent changes in transcription of genes to their mRNA levels, as well as potential gene targets regulated by TDP-43 through association with chromatin. Our analysis uncovers a potential role of TDP-43 in regulating transcription of Alu elements, a kind of short transposable element-derived repeat element. We found depletion of TDP-43 leads to a drastic increase in transcription of Alu elements throughout the genome, particularly within actively transcribed genes. We also found a general decrease in transcription of protein-coding genes that correlates with the density of actively transcribing Alu elements located within genes. Our results reveal a novel role of TDP-43 as a transcriptional repressor of Alu elements.
Degree ProgramGraduate College
Molecular & Cellular Biology