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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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Widespread RNA binding by chromatin-associated proteins.

David G Hendrickson1,2, David R Kelley3,4, Danielle Tenen5,6

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Chromatin regulators and RNA-binding proteins associate with specific RNA molecules. This widespread RNA interaction influences chromatin state and gene expression, revealing a general regulatory mechanism.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Epigenetics

Background:

  • RNA interactions are increasingly recognized as regulators of chromatin-associated protein activity and localization.
  • It remains unclear if this is a widespread phenomenon or limited to specific factors and contexts.

Purpose of the Study:

  • To investigate the general role of RNA in regulating chromatin state and gene expression.
  • To survey RNA association with a broad range of chromatin regulators and RNA-binding proteins.

Main Methods:

  • Formaldehyde RNA immunoprecipitation followed by sequencing (fRIP-Seq) was employed.
  • The study analyzed RNA association with a panel of 24 chromatin regulators and RNA-binding proteins.

Main Results:

  • 90% of tested proteins reproducibly bound significant amounts of RNA.
  • Enrichment of hundreds to thousands of noncoding and mRNA transcripts was detected for most proteins.
  • Enriched RNA sets exhibited distinct biochemical, functional, and chromatin properties for each protein.

Conclusions:

  • Evidence supports widespread, specific, and relevant RNA association with diverse chromatin-modifying complexes.
  • RNA interaction is a general mechanism underlying chromatin state establishment and gene expression regulation.