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Related Concept Videos

Telomeres and Telomerase02:41

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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence
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Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence

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Mitochondrion-processed TERC regulates senescence without affecting telomerase activities.

Qian Zheng1, Peipei Liu1, Ge Gao1

  • 1MOE Key laboratory of Bioinformatics, Cell Biology and Development Center, School of Life Sciences, Tsinghua University, Beijing, 100084, China.

Protein & Cell
|February 22, 2019
PubMed
Summary

The RNA component of Telomerase (TERC) processed in mitochondria signals cellular senescence and cognitive decline in mice, independent of telomerase activity. This reveals a novel non-coding RNA pathway regulating aging.

Keywords:
mitochondrianon-coding RNAnucleusretrograde signaltelomerasetranscription regulation

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Telomerase Activity in the Various Regions of Mouse Brain: Non-Radioactive Telomerase Repeat Amplification Protocol TRAP Assay
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Area of Science:

  • Cellular Biology
  • Neuroscience
  • Aging Research

Background:

  • Mitochondrial dysfunction is a key factor in aging.
  • The signaling pathways by which mitochondrial stress affects cellular processes are not fully understood.
  • The RNA component of Telomerase (TERC) is known to be imported into mitochondria and processed.

Purpose of the Study:

  • To investigate the role of processed TERC (TERC-53) in signaling mitochondrial function.
  • To determine if cytosolic TERC-53 influences cellular senescence and cognitive decline.
  • To elucidate a novel regulatory pathway involving non-coding RNA in aging.

Main Methods:

  • Mitochondrial import, processing, and export of TERC were analyzed.
  • Levels of cytosolic TERC-53 were correlated with mitochondrial function.
  • TERC-53 levels were manipulated in 10-month-old mice to assess effects on senescence and cognition.
  • TERC-53's role was examined in terc-/- cells.

Main Results:

  • Cytosolic TERC-53 levels reflect mitochondrial function.
  • TERC-53 regulates cellular senescence and cognitive decline in mice, independent of telomerase activity.
  • Manipulation of TERC-53 impacts hippocampal senescence and cognition.
  • TERC-53 affects cellular senescence even in the absence of telomerase (terc-/- cells).

Conclusions:

  • Cytosolic TERC-53 acts as a signal of mitochondrial function downstream of the mitochondria.
  • This study identifies a novel non-coding RNA-mediated pathway regulating cellular senescence and cognitive decline in mammals.
  • TERC-53 represents a new player in the aging process, distinct from its role in telomere maintenance.