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Open research questions in RNA Research and Splicing

697 gap statements mined from RNA Research and Splicing papers in our 7.9M-paper local library, which holds 3,018 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The role of IGF2BP1 in alternative splicing of transcription factor genes in neuroblastoma cells is unclear. The mechanisms of post-transcriptional dysregulation in neuroblastoma are not well understood.

    IGF2BP1 knockdown associates with alternative splicing changes of transcription factor genes in neuroblastoma cells · 2026 · DOI

  • The extent to which phase separation contributes to transcription is unclear. The functional benefits of phase separation, such as higher RNAP recruitment and bubble stabilization, can be achieved at the molecular scale without the requirement for large-scale liquid droplets.

    Nascent RNA-mediated recruitment and R-loop suppression underlie FUS-driven enhancement of transcription · 2026 · DOI

  • Limited literature on SEC analysis of mRNA. The need for a viable method to ensure the safety and quality of mRNA products. The lack of understanding of the interaction of nucleic acids with SEC packing materials.

    Optimizing Messenger RNA Analysis Using Ultra-Wide Pore Size Exclusion Chromatography Columns · 2024 · DOI

  • Further research could investigate the role of SAMD4A in neuronal differentiation. The study suggests that understanding the regulatory role of dynamic mRNA stability changes could provide insight into understanding gene expression.

    Dynamic mRNA Stability Buffer Transcriptional Activation During Neuronal Differentiation and Is Regulated by SAMD4A · 2024 · DOI

  • Finally, we outline open questions regarding the spatial organization of decay, PB-stress granule crosstalk, and hormonal control mechanisms, and highlight methodological avenues to address them.

    Plant P-bodies in post-transcriptional control: Composition, dynamics, and context-dependent roles · 2026 · DOI

  • Chemical tools are lacking for RBPs, which has hindered efforts to perturb and understand RBP function in cells.

    Structural and mechanistic analysis of covalent ligands targeting the RNA-binding protein NONO · 2026 · DOI

  • The molecular mechanisms that ensure their stable expression remain poorly understood.

    RNA-dependent SFPQ condensates coordinate multidimensional regulation of extra-long neuronal genes · 2026 · DOI

  • Serine/arginine-rich splicing factor 1 (SRSF1) regulates alternative splicing and acts as a proto-oncogene, but its role in transcription remains poorly defined.

    SRSF1 coordinates transcription and alternative splicing to modulate p53 and genome-maintenance · 2026 · DOI

  • Although increasing evidence suggests that transcripts associated with epithelial polarity also undergo asymmetric subcellular distribution, the trafficking patterns and regulatory mechanisms governing this process remain elusive.

    A Cis-Element in magu-2 Mediates Apical mRNA Localization via Active Transport in C. elegans · 2026 · DOI

  • While gene expression differences have been the subject of considerable focus in the evolution of sexual dimorphism, other regulatory processes remain comparatively understudied.

    Sexually dimorphic alternative splicing and its erosion following the loss of sex in stick insects · 2026 · DOI

  • The fundamental knowledge on the role of each isoform in maintaining cellular health is currently lacking.

    Impact of mRNA and protein isoforms in lipoprotein metabolism and how to modulate them · 2026 · DOI

  • However, the extent to which iPSC-CMs recapitulate native cardiac splicing patterns remains poorly understood.

    Alternative splicing dynamics during human cardiac development in vivo and in vitro · 2026 · DOI

  • This finding indicates that the absence of transcriptional differences is insufficient to conclude that a gene does not contribute functional differences between regions.

    Alternative splicing in layer 3 pyramidal neurons differs across regions of the human cortical hierarchy · 2026 · DOI

  • This review will comprehensively analyze the identified cellular functions of this novel family of secretory tuners in physiological and pathological conditions, highlighting the proposed molecular mechanisms and the remaining open questions.

    TENT5/FAM46: An Enigmatic Family of Secretory Tuners · 2025 · DOI

  • Lung cancer is the leading cause of cancer-related death worldwide, and the complex molecular mechanisms underlying its development, particularly the role of alternative splicing (AS) in different subtypes, remain poorly understood.

    Transcriptomic analysis reveals lung cancer and subtype-specific alternative splicing biomarkers regulated by RNA-binding proteins · 2025 · DOI

  • Alternative cleavage and polyadenylation (APA) is a gene regulatory mechanism used by cells under stress to upregulate proteostasis-promoting transcripts, but how cells achieve this remains poorly understood.

    Heat shock induces alternative polyadenylation through dynamic DNA methylation and chromatin looping · 2025 · DOI

  • However, the post-transcriptional regulatory mechanisms controlling tissue development and stress responses in Eucalyptus remain poorly understood.

    Profiling of the gene expression and alternative splicing landscapes of Eucalyptus grandis · 2024 · DOI

  • However, the mechanisms of the localization of Cpeb4 and osteoclastogenesis by Cpeb4 remain unknown.

    The RNA‐binding protein Cpeb4 regulates splicing of the Id2 gene in osteoclast differentiation · 2024 · DOI

  • Notably, the impact of neuronal activation on IGC/nuclear speckles organization and function remains unexplored.

    Neuronal activation affects the organization and protein composition of the nuclear speckles · 2024 · DOI

  • The evolutionary divergence in vertebrate splicing patterns has been attributed to changes in cis-regulatory splicing code elements and species-dependent differences in RNA binding protein regulators. However, the role of Alu-mediated RNA duplexes in alternative splicing patterns is not well understood.

    Alu-mediated RNA duplexes are associated with widespread exon skipping across primate transcriptomes · 2026 · DOI

  • Positional enrichment of eCLIP peaks was calculated for RBPs with consistent effects in only K562 and HepG2 cells; validation in additional cell types is needed.

    Alu-mediated RNA duplexes are associated with widespread exon skipping across primate transcriptomes · 2026 · DOI

  • However, it remains unclear why cells express so many apparently non-redundant helicases.

    Targeting R-loops: diverse RNA helicases in R-loop resolution and their potential as targets for cancer therapy · 2026 · DOI

  • The exact interplay between protein and splicing codes is, however, poorly understood.

    Copper-binding proteins and exonic splicing enhancers and silencers · 2024 · DOI

  • The study only analyzed RNA-seq data from IGF2BP1-knockdown BE(2)-C cells, - The study did not perform gene-level FDR correction, - The study used a limited number of samples…

    IGF2BP1 knockdown associates with alternative splicing changes of transcription factor genes in neuroblastoma cells · 2026 · DOI

  • Investigate the role of other RBPs in transcriptional enhancement, - Examine the role of phase separation in transcription, - Study the effects of FUS on transcription in different systems, - Investigate the relationship between FUS and other transcription…

    Nascent RNA-mediated recruitment and R-loop suppression underlie FUS-driven enhancement of transcription · 2026 · DOI

Most-cited papers in RNA Research and Splicing

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Open questions raised by papers listed on this page include: (1) The role of IGF2BP1 in alternative splicing of transcription factor genes in neuroblastoma cells is unclear (“IGF2BP1 knockdown associates with alternative splicing changes of transcription…”, 2026); (2) The extent to which phase separation contributes to transcription is unclear (“Nascent RNA-mediated recruitment and R-loop suppression underlie FUS-driven…”, 2026); (3) Chemical tools are lacking for RBPs, which has hindered efforts to perturb and understand RBP function in cells (“Structural and mechanistic analysis of covalent ligands targeting the…”, 2026); (4) The molecular mechanisms that ensure their stable expression remain poorly understood (“RNA-dependent SFPQ condensates coordinate multidimensional regulation of…”, 2026); (5) Although increasing evidence suggests that transcripts associated with epithelial polarity also undergo asymmetric subcellular distribution, the trafficking patterns and regulatory mechanisms governing this process remain elusive (“A Cis-Element in magu-2 Mediates Apical mRNA Localization via Active Transport…”, 2026). 697 gap statements have been mined from RNA Research and Splicing papers in our 7.9M-paper local library, which holds 3,018 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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