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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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Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
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Aging01:26

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Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
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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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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.
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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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Techniques to Induce and Quantify Cellular Senescence
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MicroRNA biogenesis pathway alterations in aging.

Jorge Sanz-Ros1,2, Cristina Mas-Bargues1, Nekane Romero-García1,3

  • 1Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), INCLIVA, Valencia 46010, Spain.

Extracellular Vesicles and Circulating Nucleic Acids
|December 19, 2024
PubMed
Summary
This summary is machine-generated.

Aging involves disrupted microRNA (miRNA) biogenesis, affecting gene regulation and leading to age-related diseases. Enhancing miRNA processing pathways may promote healthy aging and extend lifespan.

Keywords:
MicroRNA biogenesisaging processintercellular communicationlifespan

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Area of Science:

  • Molecular Biology
  • Genetics
  • Gerontology

Background:

  • Aging is linked to genomic instability and altered gene expression.
  • MicroRNAs (miRNAs) are key regulators of post-transcriptional gene expression.
  • Dysregulation of miRNA biogenesis is implicated in the aging process.

Purpose of the Study:

  • To investigate the impact of disrupted miRNA biogenesis on aging.
  • To explore the role of key miRNA processing enzymes and complexes in aging.
  • To connect miRNA biogenesis alterations with age-related conditions and lifespan.

Main Methods:

  • Analysis of age-related changes in miRNA transcription and processing.
  • Examination of the microprocessor complex (DGCR8/Drosha) and Dicer function during aging.
  • Review of miRNA export mechanisms (Exportin-5) in the context of aging and senescence.

Main Results:

  • Age-related genomic changes and epigenetic modifications affect primary miRNA (pri-miRNA) transcription.
  • Alterations in microprocessor complex activity and Dicer expression impact miRNA profiles during aging.
  • Interventions like caloric restriction influence microprocessor activity and are linked to lifespan extension.

Conclusions:

  • Disrupted miRNA biogenesis is a significant factor in aging and age-related diseases.
  • Targeting miRNA biogenesis pathways offers potential therapeutic strategies for healthy aging.
  • Understanding miRNA processing is crucial for developing interventions to promote longevity.