Intron Retention (IR): RNA Processing, Post-Transcriptional Regulation in Stress Response, Genomic Function

Dear Colleagues,

Intron retention (IR) has emerged as a prevalent and regulated mode of RNA processing rather than a mere splicing byproduct. Across diverse stress conditions—oxidative, genotoxic, inflammatory, metabolic, proteotoxic, hypoxic, and mechanical—IR can reshape gene output by modulating nuclear detention, mRNA stability, translation competence, and the balance between productive and non-productive isoforms. Increasing evidence links stress-responsive IR programs to cell-fate decisions, immune adaptation, tissue regeneration, aging, and disease, including cancer, neurodegeneration, cardiometabolic disorders, and infection.

This Special Issue welcomes original research, reviews, and methodological advances that elucidate mechanisms, functions, and translational implications of IR. We particularly encourage studies integrating multi-omics and modern transcriptomics (long-read sequencing, single-cell/spatial approaches), quantitative modeling, and rigorous computational frameworks for IR detection and interpretation. This Special Issue will cover a wide range of research topics, such as the following:

• Mechanistic control of IR under stress: co-transcriptional splicing kinetics, Pol II elongation, chromatin/epigenetic coupling, and spliceosome dynamics.
• Neuropsychiatric and neurodegenerative applications: IR-based biomarkers for depression and dementia, including patient stratification and treatment-response monitoring.
• Stress signaling to splicing: ISR/ATF4, MAPK, mTOR, NF-κB, and post-translational regulation of splicing factors/RBPs.
• IR as an RNA output gate: nuclear detention/export licensing, RNA surveillance (NMD), mRNA stability, and translation competence.
• Cis–trans logic of IR: regulatory elements, RNA structure, and SR/hnRNP networks shaping IR propensity and specificity.
• Subcellular RNA fate programs: stress granules/P-bodies, phase separation, and translational reprogramming in acute vs chronic stress.
• Proteostasis, redox, and metabolism: coupling of IR to UPS/ER stress, mitochondrial function, oxidative stress, and metabolic remodeling.
• Genome maintenance links: IR responses to DNA damage/replication stress and consequences for cell-cycle and genome stability.
• Mechanobiology and IR: cytoskeletal tension, focal-adhesion pathways, nuclear lamina mechanics, and mechanotransduction impacts on RNA processing.
• Immune context: IR programs in thymus/spleen/lymph nodes and immune-state transitions (tolerance, inflammation, immunometabolism).

Dr. Norihiro Okada
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the Special Issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.