Role of CYTOR long non-coding RNA in the control of transcription elongation

  • Meredith, Dawn D.C. (PI)
  • Taube, Ran (PI)
  • Schwartz, Jacob J. (CoPI)

Project Details


Gene transcription by the RNA Polymerase II (Pol II) is a key step in the overall program of gene expression of human cells, therefore is tightly regulated at numerous checkpoints along the transcription cycle. Extensive research has been conducted on the role of proteins that control transcription. In contrast, the function of non-coding genes - ncRNA (i.e., genes that do not code for proteins) is less understood. The overall goal of this study is to understand how ncRNAs optimize the function of Pol II to promote gene transcription. Specifically, we will focus our efforts on the step of transcription elongation, which is a critical step of the transcription cycle.

Towards this goal, we have been studying the regulation of gene transcription of Human Immunodeficiency Virus (HIV), which is heavily regulated by Pol II transcription elongation. In our preliminary experiments, we compared the expression levels of ncRNA in cells that are infected with either active or silenced HIV. Among several ncRNAs that were differentially and significantly expressed following HIV stimulation, we identified the Cytoskeleton Regulator RNA, CYTOR, and demonstrated its ability to activate HIV gene transcription. We present additional new results that show that CYTOR associates with protein factors of the transcription complex, specifically with the Positive Transcription Elongation Factor b, P-TEFb. CYTOR recruits P-TEFb to the HIV genome and supports activation of transcription. Based on these results, we hypothesize that through binding to P-TEFb, CYTOR promotes activation of gene transcription. We propose to confirm direct interactions between CYTOR and P-TEFb and validate the genome-wide occupancy of CYTOR on chromatin. This will allow us to identify novel downstream targets of CYTOR and understand their role in controlling global gene expression.

Our study will advance the overall understanding of the involvement of ncRNAs in controlling Pol II transcription elongation and will help in identifying novel proteins that interact with the non-coding transcriptome and regulate this step. Based on these findings, tools that target ncRNA will be developed for treating human disorders where ncRNAs play key roles.

Effective start/end date1/10/2030/09/23


  • United States-Israel Binational Science Foundation (BSF)


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