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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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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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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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Regulation of Expression at Multiple Steps01:23

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Cut from the same cloth: RNAs transcribed from regulatory elements.

E M Stasevich1, A V Simonova2, E A Bogomolova3

  • 1Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.

Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms
|July 4, 2024
PubMed
Summary
This summary is machine-generated.

Regulatory element RNAs (regRNAs) are crucial for gene regulation and cellular processes, not just transcriptional noise. This review covers diverse regRNAs and their potential as disease biomarkers and therapeutic targets.

Keywords:
Enhancer RNAInsulator RNAOncogenesisPromoter RNARegulatory elementSilencer RNA

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Area of Science:

  • Molecular Biology
  • Genomics
  • Epigenetics

Background:

  • Chromatin accessibility is essential for gene transcription.
  • Regulatory element RNAs (regRNAs) are synthesized from active genomic regions.
  • The functional significance of regRNAs is increasingly recognized, challenging the notion of transcriptional noise.

Purpose of the Study:

  • To review the diverse roles of regRNAs in human cellular processes.
  • To highlight both well-studied (promoter RNAs, enhancer RNAs) and less-studied (silencer RNAs, insulator RNAs) regRNAs.
  • To discuss the potential of regRNAs as biomarkers and therapeutic targets for human diseases.

Main Methods:

  • Literature review of studies on regRNAs.
  • Analysis of diverse classes of regRNAs, including promoter RNAs, enhancer RNAs, silencer RNAs, insulator RNAs, miRNAs, snRNAs, and snoRNAs.
  • Discussion of the implications of regRNA functions in cellular processes and diseases.

Main Results:

  • RegRNAs play multifaceted roles in human cells, extending beyond transcriptional noise.
  • Specific examples of regRNAs, including promoter RNAs, enhancer RNAs, silencer RNAs, and insulator RNAs, are discussed.
  • Shorter regRNAs such as miRNAs, snRNAs, and snoRNAs are confirmed to have important functions.

Conclusions:

  • RegRNAs are critical functional molecules involved in various cellular activities.
  • Understanding regRNA diversity and function is essential for comprehending gene regulation.
  • RegRNAs hold significant promise as biomarkers and therapeutic targets for diseases like cancer.