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MicroRNAs01:22

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
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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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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...
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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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A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
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Granzyme mRNA-miRNA interaction and its implication to functional impact.

Hyeon-Young Kim1, Jung-Min Kim2, Young Kee Shin3,4

  • 1Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea.

Genes & Genomics
|November 11, 2024
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Summary

This study reveals that specific microRNAs (miRNAs) and transcription factors regulate granzyme gene expression, impacting cancer development. Understanding these granzyme-miRNA-transcription factor networks is key to cancer suppression and treatment strategies.

Keywords:
CancerGene expressionGranzymeTranscription factormiRNA

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Area of Science:

  • Immunology and Molecular Biology
  • Cancer Genomics and Bioinformatics

Background:

  • Granzyme activity influences microRNA (miRNA) processing, stability, and expression, potentially affecting apoptotic signaling and inflammation.
  • Granzyme-induced apoptosis can alter miRNA profiles, further modulating apoptosis and inflammatory responses.

Purpose of the Study:

  • To bioinformatically analyze miRNA and transcription factor interactions with granzyme gene coding (CDS) and untranslated regions (UTR).
  • To investigate the role of these interactions in granzyme gene regulation, evolution, and association with human cancers.

Main Methods:

  • Analysis of granzyme gene expression patterns across human tissues.
  • Identification of miRNAs and transcription factors binding to granzyme mRNA regions.
  • Network visualization and analysis using Cytoscape.
  • Investigation of evolutionary patterns of granzyme family interactions.

Main Results:

  • GZMA and GZMK show high expression in lymph nodes; GZMB in bone marrow; GZMA in spleen.
  • hsa-miR-146a-5p is the sole miRNA binding to GZMK, GZMB, GZMM, and GZMA mRNA.
  • Specific transcription factors (JUND, FOS, JUN) interconnect with has-miR-5696 and GZMK.
  • Cancer association data revealed consistent miRNA involvement with granzyme family genes, showing upregulation or downregulation.

Conclusions:

  • The granzyme family exhibits high expression in immune-related tissues (lymph node, spleen, bone marrow).
  • Numerous miRNAs and transcription factors specifically regulate granzyme gene expression.
  • Elucidating the granzyme-miRNA-transcription factor network offers critical insights into cancer development and suppression mechanisms.