ArticleFrontiers in cell and developmental biology2015
Rethinking gene regulatory networks in light of alternative splicing, intrinsically disordered protein domains, and post-translational modifications.
Article in Frontiers in cell and developmental biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 122 citations in OpenAlex.
- MYB Factors: Hubs of Plant Stress and Hormone Crosstalk.Plant biotechnology journal · 2026Review
- Nitric oxide drives proteomic diversity through alternative splicing.Molecular cell · 2026Article
- Specificity of the stabilizing interaction between intrinsically disordered protein sequences and G-quadruplexes in RNA.Nucleic acids research · 2026Article
- Developmental system drift and modular gene regulatory networks shape gastrulation inLife science alliance · 2025Article
- Identification of UBA7 expression downregulation in myelodysplastic neoplasm with SF3B1 mutations.Scientific reports · 2025Article
- The role of intrinsically disordered regions of SARS-CoV-2 nucleocapsid and non-structural protein 1 proteins.Frontiers in chemistry · 2025Review
- RNA Splicing Aberrations in Hereditary Cancer: Insights from Turkish Patients.Current issues in molecular biology · 2024Article
- Alternative splicing dynamically regulates common carp embryogenesis under thermal stress.BMC genomics · 2024Article
- The molecular basis for cellular function of intrinsically disordered protein regions.Nature reviews. Molecular cell biology · 2024Review
- IndiSPENsable for X Chromosome Inactivation and Gene Silencing.Epigenomes · 2023Review
- PacBio single-molecule long-read sequencing provides new insights into the complexity of full-length transcripts in oriental river prawn, macrobrachium nipponense.BMC genomics · 2023Article
- Article
- ILF3 prion-like domain regulates gene expression and fear memory under chronic stress.iScience · 2023Article
- Review
- Alternative splicing: transcriptional regulatory network in agroforestry.Frontiers in plant science · 2023Review
- Intrinsically Disordered Proteins: Critical Components of the Wetware.Chemical reviews · 2022Review
- Cancer progression as a learning process.iScience · 2022Review
- Intrinsically disordered proteins: Ensembles at the limits of Anfinsen's dogma.Biophysics reviews · 2022Review
- Machine learning for multi-omics data integration in cancer.iScience · 2022Review
- Intrinsically disordered proteins play diverse roles in cell signaling.Cell communication and signaling : CCS · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Models for genetic regulation and cell fate specification characteristically assume that gene regulatory networks (GRNs) are essentially deterministic and exhibit multiple stable states specifying alternative, but pre-figured cell fates. Mounting evidence shows, however, that most eukaryotic precursor RNAs undergo alternative splicing (AS) and that the majority of transcription factors contain intrinsically disordered protein (IDP) domains whose functionalities are context dependent as well as subject to post-translational modification (PTM). Consequently, many transcription factors do not have fixed cis-acting regulatory targets, and developmental determination by GRNs alone is untenable. Modeling these phenomena requires a multi-scale approach to explain how GRNs operationally interact with the intra- and intercellular environments. Evidence shows that AS, IDP, and PTM complicate gene expression and act synergistically to facilitate and promote time- and cell-specific protein modifications involved in cell signaling and cell fate specification and thereby disrupt a strict deterministic GRN-phenotype mapping. The combined effects of AS, IDP, and PTM give proteomes physiological plasticity, adaptive responsiveness, and developmental versatility without inefficiently expanding genome size. They also help us understand how protein functionalities can undergo major evolutionary changes by buffering mutational consequences.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.