A dynamic compositional equilibrium governs mRNA recognition by eIF3.

Eukaryotic translation initiation factor (eIF) 3 is a multi-subunit protein complex that binds both ribosomes and messenger RNAs (mRNAs) to drive a diverse set of mechanistic steps during translation of an mRNA into the protein it encodes. And yet, a unifying framework explaining how eIF3 performs these numerous activities is lacking. Using single-molecule light scattering microscopy, we demonstrate that eIF3 is in dynamic exchange between the full complex, subcomplexes, and subunits.

Evidence, probability and relative plausibility.

A comparison is made between probability and relative plausibility as approaches for the interpretation of evidence. It is argued that a probabilistic approach is capable of answering the criticisms of the proponents of relative plausibility. It is also shown that a probabilistic approach can answer the problem of overlapping where there is evidence that each side claims supports its theory of what happened.

Corrigendum: eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5'-Untranslated Regions.

[This corrects the article DOI: 10.3389/fmolb.2021.

eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5'-Untranslated Regions.

Translation initiation in eukaryotes is a multi-step pathway and the most regulated phase of translation. Eukaryotic initiation factor 3 (eIF3) is the largest and most complex of the translation initiation factors, and it contributes to events throughout the initiation pathway. In particular, eIF3 appears to play critical roles in mRNA recruitment.

A generalised Bayes' factor formula for evidence evaluation under activity level propositions: Variations around a fibres scenario.

Generalised Bayes' factors and associated Bayesian networks are developed for the transfer of extrinsic evidence at the activity level, developments that extend previous work on activity level evaluation. A strategy for the assessment of extrinsic evidence is developed in stages with progressive increases in complexity. The final development is illustrated with an example involving fibres from clothing.

The evaluation of evidence for microspectrophotometry data using functional data analysis.

Microspectrophotometry data arise in the study of many forensically applicable situations. The situations here are those of ink and fibres. In a criminal investigation, data associated with a crime scene are compared with data associated with a person of interest.

Reasoning under uncertainty.

Introduction: It is difficult to reason correctly when the information available is uncertain. Reasoning under uncertainty is also known as probabilistic reasoning.

Methods: We discuss probabilistic reasoning in the context of a medical diagnosis or prognosis.

Bayesian Hierarchical Random Effects Models in Forensic Science.

Statistical modeling of the evaluation of evidence with the use of the likelihood ratio has a long history. It dates from the Dreyfus case at the end of the nineteenth century through the work at Bletchley Park in the Second World War to the present day. The development received a significant boost in 1977 with a seminal work by Dennis Lindley which introduced a Bayesian hierarchical random effects model for the evaluation of evidence with an example of refractive index measurements on fragments of glass.

Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity.

eIF4A is a DEAD-box RNA-dependent ATPase thought to unwind RNA secondary structure in the 5'-untranslated regions (UTRs) of mRNAs to promote their recruitment to the eukaryotic translation pre-initiation complex (PIC). We show that eIF4A's ATPase activity is markedly stimulated in the presence of the PIC, independently of eIF4E•eIF4G, but dependent on subunits i and g of the heteromeric eIF3 complex. Surprisingly, eIF4A accelerated the rate of recruitment of all mRNAs tested, regardless of their degree of structural complexity.

Rps3/uS3 promotes mRNA binding at the 40S ribosome entry channel and stabilizes preinitiation complexes at start codons.

The eukaryotic 43S preinitiation complex (PIC) bearing Met-tRNA in a ternary complex (TC) with eukaryotic initiation factor (eIF)2-GTP scans the mRNA leader for an AUG codon in favorable "Kozak" context. AUG recognition provokes rearrangement from an open PIC conformation with TC bound in a state not fully engaged with the P site ("P") to a closed, arrested conformation with TC tightly bound in the "P" state. Yeast ribosomal protein Rps3/uS3 resides in the mRNA entry channel of the 40S subunit and contacts mRNA via conserved residues whose functional importance was unknown.

A comment on the PCAST report: Skip the "match"/"non-match" stage.

This letter comments on the report "Forensic science in criminal courts: Ensuring scientific validity of feature-comparison methods" recently released by the President's Council of Advisors on Science and Technology (PCAST). The report advocates a procedure for evaluation of forensic evidence that is a two-stage procedure in which the first stage is "match"/"non-match" and the second stage is empirical assessment of sensitivity (correct acceptance) and false alarm (false acceptance) rates. Almost always, quantitative data from feature-comparison methods are continuously-valued and have within-source variability.

Eukaryotic translation initiation factor 3 plays distinct roles at the mRNA entry and exit channels of the ribosomal preinitiation complex.

Eukaryotic translation initiation factor 3 (eIF3) is a central player in recruitment of the pre-initiation complex (PIC) to mRNA. We probed the effects on mRNA recruitment of a library of eIF3 functional variants spanning its 5 essential subunits using an in vitro-reconstituted system. Mutations throughout eIF3 disrupt its interaction with the PIC and diminish its ability to accelerate recruitment to a native yeast mRNA.

Conformational Differences between Open and Closed States of the Eukaryotic Translation Initiation Complex.

Translation initiation in eukaryotes begins with the formation of a pre-initiation complex (PIC) containing the 40S ribosomal subunit, eIF1, eIF1A, eIF3, ternary complex (eIF2-GTP-Met-tRNAi), and eIF5. The PIC, in an open conformation, attaches to the 5' end of the mRNA and scans to locate the start codon, whereupon it closes to arrest scanning. We present single particle cryo-electron microscopy (cryo-EM) reconstructions of 48S PICs from yeast in these open and closed states, at 6.

On the use of the likelihood ratio for forensic evaluation: response to Fenton et al.

This letter to the Editor comments on the article When 'neutral' evidence still has probative value (with implications from the Barry George Case) by N. Fenton et al. [[1], 2014].

The evaluation of evidence relating to traces of cocaine on banknotes.

Banknotes can be seized from crime scenes as evidence for suspected association with illicit drug dealing. Tandem mass spectrometry data are available from banknotes seized in criminal investigations, as well as from banknotes from general circulation. The aim of the research is to evaluate the support provided by the data gathered in a criminal investigation for the proposition that the banknotes from which the data were obtained are associated with a person who is associated with a criminal activity related to cocaine in contrast to the proposition that the banknotes are associated with a person who is not associated with a criminal activity involving cocaine.

Information-theoretical assessment of the performance of likelihood ratio computation methods.

Performance of likelihood ratio (LR) methods for evidence evaluation has been represented in the past using, for example, Tippett plots. We propose empirical cross-entropy (ECE) plots as a metric of accuracy based on the statistical theory of proper scoring rules, interpretable as information given by the evidence according to information theory, which quantify calibration of LR values. We present results with a case example using a glass database from real casework, comparing performance with both Tippett and ECE plots.

Evidence evaluation for discrete data.

Methods for the evaluation of evidence in the form of measurements by means of the likelihood ratio are becoming more widespread. There is a paucity of methods for the evaluation of evidence in the form of counts by means of the likelihood ratio. Two suggestions for such methods are described.

The impact of aminoglycosides on the dynamics of translation elongation.

Inferring antibiotic mechanisms on translation through static structures has been challenging, as biological systems are highly dynamic. Dynamic single-molecule methods are also limited to few simultaneously measurable parameters. We have circumvented these limitations with a multifaceted approach to investigate three structurally distinct aminoglycosides that bind to the aminoacyl-transfer RNA site (A site) in the prokaryotic 30S ribosomal subunit: apramycin, paromomycin, and gentamicin.

A mechanistic overview of translation initiation in eukaryotes.

Translation initiation in eukaryotes is a complex and highly regulated process requiring the action of at least 12 protein factors. The pathway is distinguished by the formation of a pre-initiation complex that recruits the 5' end of the mRNA and scans along it to locate the start codon. During the past decade, a combination of genetics, biochemistry and structural studies has begun to illuminate key molecular events in this critical phase of gene expression.