Related Experiment Video
Updated: Jul 19, 2025
08:56
A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
11.0K
Modulation of translational decoding by m6A modification of mRNA
Sakshi Jain1, Lukasz Koziej2, Panagiotis Poulis1
1Max Planck Institute for Multidisciplinary Sciences, Göttingen, 37077, Germany.
Nature Communications
|August 8, 2023
Summary
N6-methyladenosine (m6A) modifies mRNA, impacting bacterial translation. This m6A modification hinders ribosome decoding by destabilizing complexes and increasing tRNA drop-off, affecting protein synthesis.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- N6-methyladenosine (m6A) is a prevalent mRNA modification influencing mRNA metabolism.
- m6A within mRNA coding regions is known to inhibit translation elongation.
Purpose of the Study:
- To elucidate the mechanism by which m6A modulates decoding in bacterial translation systems.
- To investigate the impact of m6A on ribosome-mRNA-tRNA interactions during translation.
Main Methods:
- Utilized a combination of rapid kinetics, single-molecule Förster Resonance Energy Transfer (smFRET), and single-particle cryo-electron microscopy (cryo-EM).
- Analyzed the stability of ribosome complexes and tRNA drop-off rates in the presence and absence of m6A.
- Examined mRNA codon conformation and its remodeling upon aminoacyl-tRNA binding.
Main Results:
- m6A does not impede the initial binding of aminoacyl-tRNA to the ribosome.
- Fewer ribosomes successfully complete decoding in the presence of m6A due to reduced complex stability and increased tRNA drop-off.
- m6A favors dynamic mRNA codon conformations that are less compatible with canonical codon-anticodon pairing and are rejected by the ribosome.
Conclusions:
- m6A modifications, even outside the direct codon-anticodon interaction site, can interfere with base pairing and ribosome recognition.
- These interactions modulate translational efficiency by affecting decoding fidelity and complex stability.
- The study reveals a novel mechanism by which mRNA modifications regulate gene expression at the translational level.
Related Concept Videos
01:23Regulation of Expression at Multiple Steps
944
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...
944
02:51mRNA Stability and Gene Expression
5.6K
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
Cis-acting Elements involved in mRNA stability
5.6K
02:27Nonsense-mediated mRNA Decay
10.7K
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,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.7K
02:24Regulation of Expression Occurs at Multiple Steps
22.8K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.8K
01:29Translational Regulation
45
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
45
01:35Pre-mRNA Processing: Modification of pre-mRNA Ends
9.5K
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
9.5K