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Related Concept Videos

Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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 addition of a...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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 dimers that...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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 dimers that...
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
Riboswitches01:56

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...

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PAR-CliP - A Method to Identify Transcriptome-wide the Binding Sites of RNA Binding Proteins
12:24

PAR-CliP - A Method to Identify Transcriptome-wide the Binding Sites of RNA Binding Proteins

Published on: July 2, 2010

TERRA transcripts are bound by a complex array of RNA-binding proteins.

Isabel López de Silanes1, Martina Stagno d'Alcontres, Maria A Blasco

  • 1Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.

Nature Communications
|October 27, 2010
PubMed
Summary

Researchers identified RNA-binding proteins that bind to telomeric repeat-containing RNA (TERRA). Downregulating these proteins affects TERRA levels, location, and telomere length, impacting telomere biology and diseases like cancer and aging.

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Published on: August 18, 2018

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Telomeres, the protective caps of chromosomes, are transcribed into telomeric repeat-containing RNA (TERRA).
  • TERRA abundance is influenced by various factors including development, telomere length, stress, and chromatin structure.
  • The precise molecular mechanisms regulating TERRA levels remain largely unelucidated.

Purpose of the Study:

  • To identify endogenous RNA-binding proteins (RBPs) that bind to TERRA in primary mouse embryonic fibroblasts.
  • To investigate the functional role of these TERRA-associated RBPs in regulating TERRA abundance, localization, and telomere length.

Main Methods:

  • Biotin pull-down assays coupled with LC-MALDI TOF/TOF mass spectrometry were employed to identify TERRA-binding proteins.
  • Small interfering RNA (siRNA) was used to downregulate specific TERRA-bound RBPs.

Main Results:

  • Several RNA-binding proteins, notably members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, were identified as abundant TERRA binders.
  • Downregulation of these RBPs significantly impacted TERRA abundance and localization within the cell.
  • TERRA-RBP modulation also affected telomere lengthening, indicating a role in telomere maintenance.

Conclusions:

  • This study reveals a novel set of RBPs that interact with TERRA, providing insights into TERRA regulation.
  • TERRA-associated RBPs play a crucial role in controlling TERRA levels and influencing telomere biology.
  • These findings suggest potential therapeutic targets for telomere-related diseases such as cancer and aging.