Open research questions in RNA Research and Splicing
148 unresolved questions extracted from the limitations and future-work sections of 374 RNA Research and Splicing papers in our library. Each links back to the study that raised it.
What the literature leaves open
Investigating the molecular mechanism of assemblysome formation, - examining the molecular basis of the nuclear enrichment of the expressed fusion protein
Optogenetic Evidence for the Intrinsic Phase Separation Propensity of the Sgs1 N-Terminal Region: Implications for Assemblysome Formation · 2026 · DOIReducing noise in exon counts and splice-junction read data. Interpreting results due to the advanced differentiation state and structural complexity of human brain tissue. Limited ability of SH-SY5Y cells to fully recapitulate mature neuronal splicing programs.
Assessment of microexon-associated junction usage in Parkinson’s disease and spinocerebellar Ataxia type 3 · 2026 · DOImRNA structure clearly modulates translation efficiency for individual transcripts, yet its role in coordinating translation across many transcripts remains poorly defined.
Recent studies have revealed that DNA can undergo protein-free phase separation in the presence of divalent cations, yet the underlying molecular mechanisms, including the interplay of base stacking, base pairing, electrostatics, and ion interactions, remain poorly understood.
However, the molecular mechanisms linking mTOR dysregulation to cerebrovascular dysfunction in AD remain poorly understood we assessed cerebrovascular levels of RNA-regulatory proteins in hAPP(J20) mice treated with rapamycin from 6 to 12 months of age.
Although multiple mechanisms have been implicated in docetaxel resistance, the upstream regulatory pathways coordinating these phenotypes remain incompletely understood.
Nucleoli are liquid-like condensates whose size is actively conserved--they remain small, numerous, and resistant to coalescence--yet the molecular mechanisms that constrain their fusion remain poorly understood.
Long noncoding RNAs (lncRNAs) are well recognized as regulators of neuronal development and function, yet their integration into canonical axonal transport pathways, an essential component of spatial gene regulation in highly polarized cells, remains incompletely defined.
nHOTAIRM1 scaffolds ANXA11-dependent assemblies to drive axonal mRNA localization in human motor neurons · 2026 · DOIBiomolecular condensates provide dynamic environments that store and organize proteins, yet the fundamental principles determining whether condensation promotes or suppresses irreversible protein aggregation remain unclear.
A conformational switch governs the dual role of liquid-liquid phase separation in amyloid fibrillization · 2026 · DOIDespite this, relatively few studies have investigated the functional impacts of human-specific alternative splicing.
Alternative polyadenylation (APA) generates mRNA isoforms with variable 3'UTR lengths, yet its genetic basis and functional significance at the population level remain unexplored in plants.
Pan‐genomic analysis of alternative polyadenylation reveals a 3′UTR remodeling regulatory layer controlling salt tolerance in rice · 2026 · DOIOur platform thus has the potential to address fundamental open questions within the field and to discover mechano-responsive targets to enhance fracture healing.
Spatial transcriptomics in bone mechanomics: Exploring the mechanoregulation of fracture healing in the era of spatial omics · 2025 · DOIHowever, these material properties remain poorly understood due to the challenges of in vivo measurements.
Micropipette aspiration reveals differential RNA-dependent viscoelasticity of nucleolar subcompartments · 2025 · DOIMuch remains to be understood regarding how the complex interplay of base stacking, base pairing, electrostatics, ion interactions, and particularly structural propensities governs RNA phase behavior.
Driving forces of RNA condensation revealed through coarse-grained modeling with explicit Mg 2+ · 2025 · DOINumerous aberrant splicing events are implicated in tumor progression, yet comprehensive reports on splicing factors and events associated with peritoneal metastasis in gastric cancer (GCPM) are lacking.
Targeting PTBP3‐Mediated Alternative Splicing of COX11 Induces Cuproptosis for Inhibiting Gastric Cancer Peritoneal Metastasis · 2025 · DOIAlthough tandem CCCH ZF (TZF) proteins have been extensively studied, their molecular functions remain poorly understood.
The non-tandem CCCH zinc finger protein AtC3H26 modulates salt stress response and phosphate starvation response through its ribonuclease activity in Arabidopsis · 2025 · DOIHowever, the molecular mechanism through which BmMasc transduces the masculinizing signal to the BmdsxM production remains unknown.
Vertebrate oocyte polarity has been observed for two centuries and is essential for embryonic axis formation and germline specification, yet its underlying mechanisms remain unknown.
The Balbiani body is formed by microtubule-controlled molecular condensation of Buc in early oogenesis · 2025 · DOIThe regulatory networks and key players involved in the pathogenesis of diabetic cardiomyopathy are not clearly known.
Interaction networks among miRNA, protein, and metabolite fingerprints identify the regulatory networks and key players in the pathogenesis of diabetic cardiomyopathy · 2025 · DOIThe mechanisms through which heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) contributes to innate immune gene regulation are poorly understood.
Myeloid-specific HNRNPA2B1 deficiency disrupts macrophage function and in vivo responses · 2025 · DOIWhile global translation is crucial for effector function, the role of selective mRNA translation in T cell homeostasis remains unclear.
Ribonuclease inhibitor 1 (RNH1) mediated mRNA specific translation regulates peripheral CD8+ T- cell homeostasis 3544 · 2025 · DOIDespite significant advances in understanding the driving forces behind LLPS, the specific impact of different types of interactions on phase separation behaviors remains underexplored.
Unraveling the impact of interaction types on phase separation of intrinsically disordered protein chains · 2025 · DOIHowever, its role in regulating gene expression and alternative splicing in hepatocellular carcinoma (HCC) remains inadequately understood.
SF3B4 regulates proliferation and apoptosis in hepatocellular carcinoma via alternative splicing and interaction with TRIM28 and SETD5 · 2025 · DOIBeyond valency, the physical features of folded domains that promote phase separation are poorly understood.
Splicing factor 3a subunit 2 (SF3A2), a poorly defined splicing factor, was notably elevated in TNBC tissues and promoted TNBC progression, as confirmed by cell proliferation, colony formation, transwell migration, and invasion assays.
SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1 · 2024 · DOI
Most-cited papers in RNA Research and Splicing
- Alternative isoform regulation in human tissue transcriptomes · Nature · 2008 · 4,553 citations
- The Transcriptional Landscape of the Mammalian Genome · Science · 2005 · 2,966 citations
- Coactivator condensation at super-enhancers links phase separation and gene control · Science · 2018 · 2,578 citations
- Blooms Like It Hot · Science · 2008 · 2,501 citations
- An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells · Nature · 2000 · 2,326 citations
- 3′ Non-coding region sequences in eukaryotic messenger RNA · Nature · 1976 · 2,055 citations
- Mechanisms of gene silencing by double-stranded RNA · Nature · 2004 · 2,038 citations
- Liquid–liquid phase separation drives cellular function and dysfunction in cancer · Nature reviews. Cancer · 2022 · 443 citations
- rMATS-turbo: an efficient and flexible computational tool for alternative splicing analysis of large-scale RNA-seq data · Nature Protocols · 2024 · 253 citations
- Possibilities and limitations of antisense oligonucleotide therapies for the treatment of monogenic disorders · Communications Medicine · 2024 · 234 citations
Most recent work
- Nuclear speckles enable processing of RNA from GC-rich isochores · Cell · 2026
- A genetically encoded device for transcriptome storage in mammalian cells · Science · 2026
- A transcription-driven microgel network poised near the sol-gel transition · bioRxiv · 2026
- Mechanisms linking cytoplasmic decay of translation-defective mRNA to transcriptional adaptation · Science · 2026
- Viscoelasticity and interface properties of multi-component condensates govern protein sequestration and suppression of amyloid formation · bioRxiv · 2026
- Susceptibility and Regulation of Biomolecular Condensates by Solutes · bioRxiv · 2026
- Analysis of RNA processing directly from spatial transcriptomics data reveals previously unknown regulation · bioRxiv · 2026
- The regulatory principles, physiological functions, and phase transition of biomolecular condensates · Frontiers in Cell and Developmental Biology · 2026
- Farnesylation-driven KRAS phase separation promotes colon tumor growth · Cell · 2026
- RNA editing controls gene drive by a Neurospora Spore killer · bioRxiv · 2026
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