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Related Concept Videos

lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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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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The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
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Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
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H19 Is a PERK-Regulated Long Non-Coding RNA That Fine-Tunes UPR Signalling and Inhibits Endoplasmic Reticulum

Wen Liu1, Ananya Gupta2, Michael Kerin3

  • 1Discipline of Pathology, Cancer Progression and Treatment Research Group, Lambe Institute for Translational Research, School of Medicine, University of Galway, H91TK33 Galway, Ireland.

International Journal of Molecular Sciences
|February 27, 2026
PubMed
Summary
This summary is machine-generated.

The unfolded protein response (UPR) downregulates the H19 long non-coding RNA (lncRNA) via the PERK pathway. H19 influences UPR signaling and impacts cell fate, with high expression linked to poor breast cancer prognosis.

Keywords:
H19breast cancercell deathendoplasmic reticulum stresslong non-coding RNAtriple negative breast cancerunfolded protein response

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Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The endoplasmic reticulum (ER) stress response involves the unfolded protein response (UPR) to restore homeostasis.
  • Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cellular processes, including ER homeostasis.
  • The interplay between UPR and lncRNA expression is an active area of research.

Purpose of the Study:

  • To investigate the regulation of lncRNA H19 expression during ER stress.
  • To determine the specific UPR pathway mediating H19 downregulation.
  • To elucidate the functional role of H19 in UPR signaling and its implications in breast cancer.

Main Methods:

  • Utilized genetic (knockdown) and pharmacological inhibition/activation of PERK.
  • Employed cell lines including MCF7, T47D, 293T, and MDA-MB-231.
  • Performed bioinformatic analyses on breast cancer patient cohorts.

Main Results:

  • ER stress downregulates H19 lncRNA expression in a PERK-dependent manner.
  • H19 overexpression modulates ATF6, PERK, and IRE1-XBP1 UPR pathways.
  • Ectopic H19 confers resistance to ER stress-induced apoptosis in TNBC cells.
  • High H19 expression correlates with poor prognosis in breast cancer, especially basal-like subtypes.

Conclusions:

  • H19 is a novel UPR-regulated lncRNA, primarily controlled by the PERK pathway.
  • H19 plays a significant role in modulating UPR signaling and influencing cell fate under ER stress.
  • H19 represents a potential prognostic biomarker and therapeutic target in certain breast cancer subtypes.