Related Experiment Video

Updated: Jul 25, 2025

Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules
09:33

Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules

Published on: May 12, 2017

14.6K

QKI shuttles internal m7G-modified transcripts into stress granules and modulates mRNA metabolism

Zhicong Zhao1, Ying Qing2, Lei Dong2

  • 1Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Cell
|June 28, 2023
PubMed

Insights

Quaking proteins (QKIs) bind internal N7-methylguanosine (m7G) modifications on messenger RNAs (mRNAs). This interaction regulates mRNA stability and translation, impacting cancer cell chemotherapy sensitivity.

Area of Science:

  • Molecular Biology
  • RNA Modifications
  • Cancer Research

Background:

  • N7-methylguanosine (m7G) modification is crucial for mRNA processing and protein synthesis, primarily at the 5' cap.
  • The functional significance of internal m7G modifications within messenger RNAs (mRNAs) remains largely unexplored.

Purpose of the Study:

  • To investigate the role of internal m7G modifications in mRNA metabolism.
  • To identify proteins that recognize and bind internal m7G-modified mRNAs.
  • To elucidate the function of this interaction in cellular stress responses and drug resistance.

Main Methods:

  • Transcriptome-wide profiling and mapping of the internal m7G methylome.
  • Identification and characterization of Quaking protein (QKI) binding sites on m7G-modified mRNAs.
  • Co-immunoprecipitation assays to study protein-protein interactions (QKI7 and G3BP1).
  • Analysis of mRNA stability and translation efficiency under stress conditions.

Main Results:

  • Over 1,000 high-confidence internal m7G-modified and QKI-bound mRNA targets were identified, featuring a conserved "GANGAN" motif.
  • Quaking proteins (QKIs) selectively recognize and bind internal m7G-modified mRNAs.
  • QKI7 interacts with G3BP1, a stress granule core protein, and facilitates the translocation of m7G-modified transcripts into stress granules.
  • This process regulates mRNA stability and translation, particularly attenuating the translation of Hippo signaling pathway genes, thereby sensitizing cancer cells to chemotherapy.

Conclusions:

  • QKIs function as readers of internal m7G modifications on mRNAs.
  • Internal m7G modification and QKI binding play a significant role in mRNA metabolism and cellular responses to stress.
  • The QKI-QKI7-G3BP1 axis modulates mRNA translation and stability, influencing cancer cell drug resistance and sensitivity.
Keywords:
G3BP1METTL1N(7)-methylguanosineQKIdrug resistancem(7)GmRNA metabolismmRNA stabilitystress granuletranslational regulation

More Related Videos

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling10:59

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling

Published on: May 19, 2014

18.4K
Measurements of Physiological Stress Responses in C. Elegans10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

14.0K

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

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...
2.5K
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...
7.7K
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,...
10.7K
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...
3.0K
mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

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.
Cis-acting Elements involved in mRNA stability
5.7K
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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...
951