Open research questions in RNA and protein synthesis mechanisms
151 unresolved questions extracted from the limitations and future-work sections of 430 RNA and protein synthesis mechanisms papers in our library. Each links back to the study that raised it.
What the literature leaves open
further study of the structural response of viruses to a dehydrating environment, - application of single-particle imaging using XFELs to other viral capsids
The inability to study viral capsids in situ under dehydrating conditions. The lack of direct experimental evidence for the predicted low-energy buckling transitions in icosahedral capsids.
further characterization of the evolutionary relationships of highly divergent RNA viruses, - analysis of the human gut RNA virome in the context of complex diseases, - development of more accurate structural prediction methods for deeply divergent sequences
Deep learning coupled with scalable domain-specific structural validation expands RNA virus discovery from metatranscriptomes · 2026 · DOIExisting methods have limitations in detecting highly divergent viral signals. Prior work has focused on motif-centric tools that miss short fragments and deeply divergent viruses. The systematic exclusion of short sequences in current metagenomic pipelines is a fundamental limitation.
Deep learning coupled with scalable domain-specific structural validation expands RNA virus discovery from metatranscriptomes · 2026 · DOIThe need for a comprehensive study of the translation of IRES-containing mRNAs, - The possibility of artifacts due to promoter activity of the putative IRES element and other upstream sequences, - The possibility of splicing of transcripts in the nucleus to form alternative mRNAs
Reassessment of IRES Element Activity in Komagataella phaffii Using a Standardized Bicistronic System: Cryptic Promoter Activity Mimics Cap-Independent Translation · 2026 · DOIThe search for cellular IRES elements, - The characterization of heterologous viral IRES elements, - The development of a comprehensive study of the translation of IRES-containing mRNAs
Reassessment of IRES Element Activity in Komagataella phaffii Using a Standardized Bicistronic System: Cryptic Promoter Activity Mimics Cap-Independent Translation · 2026 · DOIComprehensive analyses of codon usage bias in the chloroplast genomes of Gnetales species are lacking. The factors that influence codon usage bias in Gnetales species are not well understood.
Comparative Analysis of the Codon Usage Pattern in the Chloroplast Genomes of Gnetales Species · 2024 · DOIAutoRNA demonstrates that variational autoencoders can learn meaningful coarse-grained structural representations of RNA from limited data.
Although equilibration is a critical component of umbrella sampling workflows, the impact of equilibration length on thermodynamic predictions remains poorly understood.
Longer Is Not Always Better: Effects of Equilibration Length on Umbrella Sampling Estimations for RNA Hairpin Folding Stabilities · 2026 · DOIThe coding sequence of an mRNA directs its own decay, yet how codons, codon context, and amino acids collectively regulate mRNA stability remains poorly understood.
Abstract The minute-scale lifetime of mRNA strongly influences bacterial gene expression, whereas a robust and programmable approach to directly control the mRNA stability and topology remains elusive.
How the assembling proteins distinguish viral RNA from host RNA is not fully understood, but RNA structure is thought to play a key role.
Particularly, the role of conformational dynamics in ribozyme catalysis remains elusive.
A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA · 2025 · DOI-glycosylated and terminated with sialic acids, although the glycosylation sites and potential functions remain unclear.
In Situ Visualization of RNA-Specific Sialylation on Living Cell Membranes to Explore N -Glycosylation Sites · 2024 · DOIHowever, comprehensive analyses of CUB within the chloroplast genomes of Gnetales species remain unexplored.
Comparative Analysis of the Codon Usage Pattern in the Chloroplast Genomes of Gnetales Species · 2024 · DOIRNA polymerase ribozymes (PR) - including a variant that uses trinucleotide triphosphates (triplets) as substrates - have been created by in vitro evolution and are the closest functional analogues of the replicase, but the structural basis for their function is poorly understood.
In bacteria, RNA-binding proteins (RBPs) are known to be involved in posttranscriptional regulation, but their global impact on RNA half-lives has not been extensively studied.
Improved RNA stability estimation through Bayesian modeling reveals most Salmonella transcripts have subminute half-lives · 2024 · DOIOn general grounds, the model predicts how the fraction of ribosomes in the proteome depends on total mRNA concentration and inspects an underexplored regime in which the trade-off between transcript levels and ribosome abundances sets the cellular growth rate.
The intricacies of this dynamic structure-function relationship are not well understood particularly in the context of viral infection.
Multi-omics analysis reveals the dynamic interplay between Vero host chromatin structure and function during vaccinia virus infection · 2024 · DOIOur structural bioinformatics studies not only provided insight into the differences between the hydrophobic helices and hydrophilic helices in the glutamate transporters, but they are also expected to stimulate further study of other water-soluble transmembrane proteins.
Structural bioinformatics studies of glutamate transporters and their AlphaFold2 predicted water-soluble QTY variants and uncovering the natural mutations of L->Q, I->T, F->Y and Q->L, T->I and Y->F · 2024 · DOIFurther exploration of the implications of the new model. Investigation of the role of RNA and the ribosome in the cell. Development of new therapies based on the concept of restoring balance in the recycling system.
The Ribosome, RNA, and the Architecture of the Living Cell A Revision of Conventional Molecular Biology · 2026 · DOIUncertain structure and low evolutionary constraint of microproteins. The need for improved detection and annotation methods. The complexity of the human proteome.
The number of ncORFs that represent true protein-coding genes is a subject of controversy. Few microproteins have been annotated as canonical proteins by reference annotation catalogues.
The need for a lightweight adapter to transform DNA language models into effective RNA analyzers. The need for a principled path toward unifying genomic language modeling.
The detection of the ppGpp effect on TL folding relies on distributions of ePEC conformations that include TL-folded states and not direct detection of ppGpp action on the NAC. Computational sorting of particles to distinct conformational states during cryo-EM data processing is inherently limited by the signal-to-noise ratio of the underlying individual particle images.
ppGpp regulates transcription elongation via direct and indirect inputs to RNA polymerase pausing and nucleotide addition · 2026 · DOI
Most-cited papers in RNA and protein synthesis mechanisms
- In vitro selection of RNA molecules that bind specific ligands · Nature · 1990 · 8,853 citations
- Role for a bidentate ribonuclease in the initiation step of RNA interference · Nature · 2001 · 3,784 citations
- Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling · Science · 2009 · 3,765 citations
- RNA interference · Nature · 2002 · 3,382 citations
- Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses · Nature · 2006 · 3,336 citations
- The multilayered complexity of ceRNA crosstalk and competition · Nature · 2014 · 3,308 citations
- The Complete Atomic Structure of the Large Ribosomal Subunit at 2.4 Å Resolution · Science · 2000 · 2,706 citations
- tRNA punctuation model of RNA processing in human mitochondria · Nature · 1981 · 2,187 citations
- Protein synthesis and memory: A review. · Psychological Bulletin · 1984 · 1,214 citations
- Algorithm for optimized mRNA design improves stability and immunogenicity · Nature · 2023 · 473 citations
Most recent work
- Expanding the human proteome with microproteins and peptideins · Nature · 2026
- Divergence between structural binding potential and cellular target engagement of neomycin on human ribosomes · bioRxiv · 2026
- Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase · Science · 2026
- tRNA isodecoder analysis using Nanopore ionic current signals and deep learning · bioRxiv · 2026
- Sequence features and dynamics of subcellular translation revealed by APEX-Ribo-Seq · bioRxiv · 2026
- A fully open structure-guided RNA foundation model for robust structural and functional inference · bioRxiv · 2026
- A new protein-dependent riboswitch activates ribosomal frameshifting · bioRxiv · 2026
- Exornata: A Web-based Tool for the Visualization and Editing of RNA Secondary Structures · Journal of Molecular Biology · 2026
- mRNA 3′ UTRs chaperone intrinsically disordered regions to control protein activity · Cell · 2026
- Membrane insertion of mitochondrial-encoded proteins regulates ribosome decoding speed · Nature Structural & Molecular Biology · 2026
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