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Biochemistry, Genetics and Molecular Biology · Research topic

Open research questions in RNA and protein synthesis mechanisms

40 unresolved questions extracted from the limitations and future-work sections of 300 RNA and protein synthesis mechanisms papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • In vitro evolution has enabled the discovery of ribozymes that catalyze diverse chemical reactions, but it is likely that many catalytic activities of RNA remain to be uncovered.

    A ribozyme ligase that requires a 3′ terminal phosphate on its RNA substrate · 2026 · DOI

  • Retrons are tripartite abortive infection systems that detect phage invasion using reverse-transcribed DNA (msDNA), but how they structurally couple threat detection to effector activation remains poorly understood.

    Higher-order assembly of a type IX retron enables exploitation for designer antimicrobials · 2026 · DOI

  • BackgroundThe regulation of mRNA decay and translation is crucial for cellular function and development; however, the complex interplay of RNA-binding proteins (RBPs) regulating these processes remains incompletely understood.

    Decoding UTRs by applying explainable AI to a genomic foundation model · 2026 · DOI

  • Coarse RNA coordinate representations are increasingly used for inverse folding and structural annotation, yet the biological information encoded in such representations is not well quantified.

    FORGE reveals an information spectrum encoded in RNA tertiary-structure geometry · 2026 · DOI

  • The -1 Programmed Ribosomal Frameshifting (-1 PRF) signal of SARS-CoV-2, driven by a conserved three-stemmed RNA pseudoknot (PK), is indispensable for viral replication and represents a structurally stable yet underexplored therapeutic target.

    Drug Functional Site-Unknown Molecular Targets Exemplified by SARS-CoV-2 pseudoknot and ribosomal frameshifting-modulators · 2026 · DOI

  • While the mechanism of 40S translocation remains elusive, the RNA helicase eIF4A has long been suspected as the primary molecular motor driving 40S scanning.

    40S ribosomal subunits move along the 5' UTR through an eIF4A-independent mechanism in higher eukaryotes · 2026 · DOI

  • Ribosomes scanning the 5UTR upstream of canonical AUG starts recognize near-cognate starts inefficiently, however, and the mechanisms by which non-canonical starts might be regulated physiologically are poorly understood.

    Amino Acid Stress Induces Non-AUG Initiation of c-myc Translation · 2026 · DOI

  • SummaryStructural comparison of nucleic acids, particularly RNA, is critical for understanding evolutionary and functional relationships beyond sequence similarity, yet efficient tools for large-scale 3D structure search and alignment remain scarce.

    Nucleic acid 3D structure search and alignment with GTalign · 2026 · DOI

  • Small molecules that target structured RNA hold therapeutic promise across a wide range of diseases, yet the structural principles governing RNA-ligand recognition remain poorly defined.

    Structural Pockets and Interacting RNA-Associated Ligands (SPIRAL): A DSSR-enabled Meta-Analysis of RNA-Small Molecule Recognition · 2026 · DOI

  • Genomic language models (gLMs) trained only on large-scale nucleic acid sequence data seem to capture signals of RNA structure, yet the specifics of how remain unclear.

    Disentangling RNA evolution and thermodynamics in genomic language models · 2026 · DOI

  • Thus, some HLA-detected ncORFs lack evidence in tryp- tic MS proteomics for either technological or biological reasons, such as the small size or amino acid composition of their encoded microproteins.

    Expanding the human proteome with microproteins and peptideins · 2026 · DOI

  • Machine learning approaches for predicting chemical shifts in molecular solids [14] have not been systematically combined with explicit solvation models in quantum chemical fragment methods for biomolecules under varying pH and ionic strength conditions.

    Using quantum chemistry to estimate chemical shifts in biomolecules · 2020 · DOI

  • The automated fragmentation approaches cited in the references do not address residual dipolar coupling calculations in RNA structures, despite their validation for carbonyl carbon and amide proton chemical shifts, leaving a gap in unified NMR property prediction for nucleic acids.

    Using quantum chemistry to estimate chemical shifts in biomolecules · 2020 · DOI

  • Conformational sampling effects on quantum chemical NMR predictions have been addressed for proteins [27], but the methodology has not been applied to characterize Watson-Crick versus Hoogsteen base pairing in DNA-protein complexes where multiple conformational states coexist.

    Using quantum chemistry to estimate chemical shifts in biomolecules · 2020 · DOI

  • The level of theory and basis set dependence documented in references [26] for isolated protein fragments has not been extended to investigate how different functional (B3LYP, OPTX, etc.) and solvation model choices affect chemical shift predictions in RNA hairpin structures and DNA-protein complexes.

    Using quantum chemistry to estimate chemical shifts in biomolecules · 2020 · DOI

  • The fragment-based QM/MM approaches for NMR chemical shift calculations (AFNMR, fragment density functional theory) have not been systematically compared across different fragmentation schemes and boundary treatments for large protein complexes exceeding 300 amino acids.

    Using quantum chemistry to estimate chemical shifts in biomolecules · 2020 · DOI

  • The data provide a valuable resource and demonstrate the power of an integrative approach to gain system-level structural insights into a poorly characterized biological system.

    Integrative structural interactomics reveals protein organization and structure in a giant virus · 2026 · DOI

  • (Meta)genomics and (meta)transcriptomics have provided insight into their diverse coding repertoire, but many of the proteins remain to be characterized as they lack homology with known proteins.

    Integrative structural interactomics reveals protein organization and structure in a giant virus · 2026 · DOI

  • Transcription start sites and mutagenesis for CJ and VSV reveal a {sigma}70 extended TGn promoter motif that is lacking in PTH.

    Transcription terminators with context-dependent promoter and terminator activities · 2026 · DOI

  • However, the structural basis by which the RT-ncRNA complex directs repeat addition processivity and controls repeat length remains unknown.

    Mechanism of tandem-repeat DNA synthesis by an antiviral reverse transcriptase · 2026 · DOI

  • Translation initiation has become an attractive target for engineering orthogonal translation systems, yet the extent to which these systems retain functionality across distinct host backgrounds remains poorly defined.

    Host background shapes the portability of a non-canonical translation initiation system across <i>Escherichia coli</i> strains · 2026 · DOI

  • The mechanisms driving membrane protein folding remain elusive, largely due to the limited availability of approaches that can probe these processes both in real-time and in their native context.

    The Shape of Things to Come: a‑Helical Membrane Protein Folding on the Ribosome · 2026

  • Using 18 natural small nuclear RNAs as examples, we show that the degree of nontrivial ultrametricity varies widely.

    Ultrametricity of Energy Minimum Configurations of RNA Secondary Structures in the Nussinov Model · 2026

  • While it is generally assumed that the assembly of these RNPs is driven by the binding of the nucleocapsid (N) protein to the gRNA in the cytoplasm, the precise molecular mechanism remains to be fully elucidated.

    A Structural Domain in the genomic RNA of SARS-CoV-2 Folds into a Compact Granular Structure without the N protein: A Single-Molecule Fluorescence Spectroscopic Investigation · 2026 · DOI

  • While snoRNAs may also interact with other RNAs, such as mRNA, the full repertoire of RNAs targeted by snoRNA remains elusive due to the lack of effective technologies that identify snoRNA targets transcriptome wide.

    snoRNA-facilitated protein secretion revealed by transcriptome-wide snoRNA target identification · 2024 · DOI

Most-cited papers in RNA and protein synthesis mechanisms

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40 open questions have been extracted from the limitations and future-work passages of 300 RNA and protein synthesis mechanisms papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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