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Regulation of Expression Occurs at Multiple Steps02:24

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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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Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
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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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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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LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
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Regulation and function of R-loops at repetitive elements.

Alice Gambelli1, Alessandro Ferrando1, Chiara Boncristiani1

  • 1Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Via E. Weiss 2, 34127, Trieste, Italy.

Biochimie
|August 24, 2023
PubMed
Summary

R-loops, structures with RNA:DNA hybrids, are crucial for genome regulation but can cause instability. Managing R-loops is vital, especially in repetitive DNA regions, to maintain genome integrity and prevent disease.

Keywords:
CentromereDiseaseR-loopsRNA:DNA hybridsRibosomeTelomereTransposable elementTriplet repeat expansion

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Area of Science:

  • Genomics
  • Molecular Biology
  • Epigenetics

Background:

  • R-loops are three-stranded nucleic acid structures involving RNA:DNA hybrids and a single-stranded DNA loop.
  • They play physiological roles in gene expression, chromatin structure, DNA repair, and replication.
  • Persistent R-loops can lead to DNA damage, genome instability, and replication-transcription conflicts.

Purpose of the Study:

  • To review the impact of R-loops on repetitive genomic regions.
  • To discuss the role of R-loops in the function and stability of centromeres, telomeres, rDNA, transposable elements, and triplet repeats.
  • To explore the pathological relevance of R-loops in associated conditions.

Main Methods:

  • Review of existing literature on R-loop biology.
  • Analysis of transcriptome data highlighting transcriptional activity in repetitive regions.
  • Integration of findings on R-loop formation, resolution, and consequences.

Main Results:

  • 85% of the human genome exhibits transcriptional activity, suggesting widespread R-loop potential.
  • Repetitive sequences, comprising 75% of the genome, are particularly susceptible to R-loop associated instability.
  • R-loops significantly impact the stability and function of key repetitive elements.

Conclusions:

  • R-loop management is critical for maintaining genome integrity, particularly in repetitive sequences.
  • Dysregulation of R-loops in repetitive regions contributes to various pathological conditions.
  • Understanding R-loop dynamics in these regions is essential for future therapeutic strategies.