Related Experiment Video
Updated: Feb 19, 2026
08:47
Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
3.4K
m6A Facilitates eIF4F-Independent mRNA Translation
Ryan A Coots1, Xiao-Min Liu2, Yuanhui Mao2
1Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; Graduate Field of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
Molecular Cell
|November 7, 2017
Summary
N6-methyladenosine (m6A) RNA modification enhances protein synthesis resistant to eIF4F inhibition, revealing a new cap-independent translation pathway. This discovery highlights the role of METTL3 and ABCF1 in cellular translation regulation.
Area of Science:
- Molecular Biology
- RNA Biology
- Cellular Biology
Background:
- Eukaryotic protein synthesis usually starts with eIF4F binding to the mRNA 5' cap.
- Despite eIF4F inhibition, overall translation output remains surprisingly robust.
- Cap-independent translation mechanisms like IRES are insufficient to explain this robustness.
Purpose of the Study:
- To investigate the mechanism behind eIF4F-resistant mRNA translation.
- To identify novel pathways regulating protein synthesis independent of cap recognition.
- To elucidate the role of RNA modifications in translation.
Main Methods:
- Investigated the role of N6-methyladenosine (m6A) in mRNA translation.
- Utilized depletion of the methyltransferase METTL3 to assess its impact on translation.
- Identified and characterized the function of ABCF1 in m6A-mediated translation.
Main Results:
- N6-methyladenosine (m6A) facilitates mRNA translation resistant to eIF4F inactivation.
- METTL3 depletion selectively inhibits translation of mRNAs with 5' UTR methylation, not TOP elements.
- ABCF1 acts as a crucial mediator for m6A-promoted translation under various conditions.
- ABCF1-sensitive transcripts significantly overlap with METTL3-dependent targets.
Conclusions:
- m6A modification drives a significant portion of cap-independent mRNA translation.
- This pathway, mediated by METTL3 and ABCF1, offers a new perspective on translational control.
- Findings challenge existing models of eukaryotic translation initiation and regulation.
Related Concept Videos
02:33Initiation of Translation
39.5K
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
39.5K
02:33Initiation of Translation
8.2K
8.2K
02:22Regulated mRNA Transport
7.1K
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...
7.1K
02:22Regulated mRNA Transport
3.4K
3.4K
02:07Improving Translational Accuracy
15.2K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
15.2K
02:28Leaky Scanning
5.8K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.8K