Related Experiment Video
Updated: Jul 28, 2025
10:37
Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
Published on: May 10, 2018
12.6K
TROP2 translation mediated by dual m
Cong Chen1, Yinghui Chao2, Chengcheng Zhang1
1Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Cancer Letters
|June 2, 2023
Summary
Dual RNA modifications, messenger RNA N6-adenosine methylation (m6A) and transfer RNA 7-methylguanosine (m7G), promote bladder cancer (BCa) by enhancing oncogene TROP2 translation. Targeting METTL3 and METTL1 inhibits BCa progression.
Area of Science:
- Molecular Biology
- Epigenetics
- Cancer Research
Background:
- RNA modifications like m6A and m7G are vital for RNA function.
- The synergistic role of dual m6A/m7G modifications in bladder cancer (BCa) gene translation is not well understood.
Purpose of the Study:
- To elucidate the mechanism of dual m6A/m7G RNA modifications in promoting TROP2 translation and BCa development.
- To investigate the therapeutic potential of targeting these RNA epigenetic pathways.
Main Methods:
- Investigated METTL3-mediated m6A modification of TROP2 mRNA and METTL1-mediated m7G modification of tRNA.
- Assessed the impact of TROP2 inhibition and METTL3/METTL1 knockout on BCa cell behavior in vitro and in vivo.
- Analyzed the correlation between TROP2, METTL3, and METTL1 expression in BCa patients.
Main Results:
- METTL3 promotes TROP2 mRNA translation via m6A modification, while METTL1 enhances it through tRNA m7G modification.
- Inhibition of TROP2 or combined knockout of METTL3/METTL1 suppressed BCa cell proliferation, invasion, and migration.
- TROP2 overexpression partially rescued the inhibitory effects of METTL3/METTL1 knockout, and TROP2 levels correlated positively with METTL3 and METTL1 in patients.
Conclusions:
- METTL3 and METTL1-mediated dual m6A/m7G RNA modifications synergistically enhance TROP2 translation, driving BCa progression.
- This study reveals a novel RNA epigenetic mechanism in bladder cancer, highlighting TROP2, METTL3, and METTL1 as potential therapeutic targets.
Related Concept Videos
01:20Cotranslational Protein Translocation
7.4K
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
7.4K
01:19Translocation of Proteins into the Mitochondria
3.2K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.2K
02:22Regulated mRNA Transport
6.3K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.3K
01:22Protein Transport to the Thylakoids
2.3K
Thylakoids are membrane-bound sac-like structures within the chloroplast that serve as sites for photosynthesis. Thylakoid lumen contains many electron transport proteins and is enclosed by a thylakoid membrane rich in the light-harvesting complex. Proteins targeted to the thylakoids are transported as precursors and are sorted by the general TOC/TIC import pathway. Once the precursor reaches the stroma, stromal processing peptidases remove their transit signal and expose thylakoid signal...
2.3K
01:29Insertion of Multi-pass Transmembrane Proteins in the RER
8.1K
The rough ER membrane synthesizes, assembles, and embeds transmembrane proteins in diverse topologies. These proteins function as transporters or channels and can remain in the ER membrane or are sent to the Golgi complex, lysosome, and cell membrane.
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
8.1K
01:39Mitochondrial Protein Sorting
4.4K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.4K