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Related Concept Videos

Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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Telomeres and Telomerase02:41

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
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Replication in Eukaryotes

In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
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Updated: May 23, 2026

Techniques to Induce and Quantify Cellular Senescence
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Published on: May 1, 2017

Ribonuclease DIS3 delays aging and senescence by generating tRNA halves.

Seokjun G Ha1, Hanseul Lee1, Jisoo Park1

  • 1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.

Nature Communications
|May 21, 2026
PubMed
Summary

Transfer RNA halves (tRHs) are generated by DIS-3/DIS3 ribonuclease, impacting aging. Specific tRHs promote longevity by reducing translation and upregulating protective factors, counteracting organismal and cellular aging.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Aging Research

Background:

  • The roles of transfer RNA halves (tRHs) in aging and longevity are not well understood.
  • tRHs are generated from cleaved transfer RNAs (tRNAs).

Purpose of the Study:

  • To investigate the role of tRHs in aging and longevity in metazoans.
  • To identify the ribonuclease responsible for tRH generation.

Main Methods:

  • Genetic screening in *Caenorhabditis elegans* to identify key enzymes.
  • Analysis of specific tRHs (e.g., 5'-tRH-Gln, 5'-tRH-Cys) and their functions.
  • Investigation of molecular mechanisms including translation regulation and transcription factor activation.
  • Examination of mammalian DIS3 function in cellular senescence.

Main Results:

  • DIS-3/DIS3 was identified as the ribonuclease catalyzing tRH generation.
  • 5'-tRH-Gln is crucial for longevity induced by interventions like dietary restriction.
  • 5'-tRH-Gln generation decreases translation and upregulates the longevity-associated SKN-1/NRF transcription factor.
  • Mammalian DIS3 generates tRHs, delaying cellular senescence via translation downregulation by 5'-tRH-Cys.

Conclusions:

  • DIS-3/DIS3 is an evolutionarily conserved ribonuclease that generates tRHs.
  • tRH generation by DIS-3/DIS3 actively counteracts both organismal and cellular aging.
  • This pathway represents a novel mechanism for lifespan regulation.