Related Experiment Video

Updated: May 31, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

Inhibition of nonsense-mediated RNA decay by the tumor microenvironment promotes tumorigenesis

Ding Wang1, Jiri Zavadil, Leenus Martin

  • 1Department of Medicine, New York University School of Medicine, 550 1st Avenue, New York, New York 10016, USA.

Molecular and Cellular Biology
|July 7, 2011
PubMed

Insights

Nonsense-mediated RNA decay (NMD) is inhibited by cellular stress via eIF2α phosphorylation, impacting tumor growth and stress response pathways. This regulation is crucial for cancer cell adaptation.

Area of Science:

  • Molecular Biology
  • Cellular Stress Response
  • Oncology

Background:

  • Nonsense-mediated RNA decay (NMD) is a key RNA surveillance pathway, but its physiological regulation and biological roles remain unclear.
  • Previous work showed NMD inhibition in hypoxic cells.
  • Cellular stress responses are critical for tumor cell survival and progression.

Purpose of the Study:

  • To investigate the regulation of NMD by cellular stress.
  • To identify NMD-targeted mRNAs and their functional relevance in stress and tumorigenesis.
  • To understand the role of NMD inhibition in tumor microenvironment adaptation.

Main Methods:

  • Investigated the effect of eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation on NMD activity.
  • Utilized unbiased approaches to identify NMD-targeted messenger RNAs (mRNAs).
  • Assessed the impact of NMD inhibition on cellular resistance to endoplasmic reticulum stress and tumor formation.

Main Results:

  • Phosphorylation of eIF2α by various cellular stresses inhibits NMD.
  • eIF2α phosphorylation and NMD inhibition are observed in tumors.
  • Identified ~750 NMD-targeted mRNAs enriched in stress response and tumor-promoting pathways.
  • NMD inhibition enhances cellular resistance to endoplasmic reticulum stress and promotes tumor formation.

Conclusions:

  • eIF2α phosphorylation is a mechanism for NMD inhibition under cellular stress.
  • NMD inhibition plays a significant role in regulating genes involved in cellular stress response and tumorigenesis.
  • The tumor microenvironment can inhibit NMD, contributing to cancer cell adaptation and progression.

More Related Videos

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

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.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
MicroRNAs01:22

MicroRNAs

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...
MicroRNAs01:22

MicroRNAs

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 ends...
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...