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Biol."],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Co-transcriptional splicing and protein self-assembly are governed by coupled kinetic and thermodynamic constraints, such that modest changes in exon processing can propagate into substantial shifts in isoform-dependent mesoscale behavior. Here, we develop a cross-scale physical framework to examine whether transcription-associated kinetic pressure could differentially bias CPEB4 microexon selection and thereby reshape downstream isoform behavior. Using a simplified transcriptional kinetic model, we define an acetylation-associated high-throughput regime as a coarse-grained proxy for reduced time available for co-transcriptional exon recognition. Comparative sequence and structural analyses identify microexon 4 (me4) as less robust than microexon 3 (me3), with weaker cis-regulatory support and lower thermodynamic stability, consistent with greater susceptibility to omission under kinetically constrained conditions. A reduced probabilistic splicing framework accordingly predicts a directional bias against me4, superimposed on a basal transcript landscape in which the full-length isoform remains present. As a complementary downstream analysis, scaled-particle-theory calculations indicate that representative \u03944-enriched scenarios thermodynamically favor homotypic self-association under macromolecular crowding, suggesting a plausible physical amplification route for modest splicing bias. Orthogonal measurements in a yeast perturbation system identify oxidative and spectroscopic signatures compatible with strong butyrate-associated physicochemical stress, but these are interpreted as perturbation readouts rather than direct measurements of neuronal histone acetylation or splicing. Together, these results define a testable cross-scale framework linking transcription-associated kinetic constraints, directional microexon susceptibility, and crowding-dependent remodeling of the CPEB4 isoform assembly landscape.<\/jats:p>","DOI":"10.1088\/1478-3975\/ae8d70","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T22:52:21Z","timestamp":1784587941000},"page":"046002","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A cross-scale physical framework for transcription-associated CPEB4 microexon susceptibility and crowding-enhanced isoform self-association: toward a biophysical mechanism of idiopathic autism"],"prefix":"10.1088","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2709-409X","authenticated-orcid":false,"given":"Ysa\u00edas J","family":"Alvarado","sequence":"first","affiliation":[{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7400-2950","authenticated-orcid":false,"given":"Arlene","family":"Cardozo-Urdaneta","sequence":"additional","affiliation":[{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6750-8712","authenticated-orcid":true,"given":"Alejandro","family":"Vivas","sequence":"additional","affiliation":[{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3346-7101","authenticated-orcid":false,"given":"Carla","family":"Lossada","sequence":"additional","affiliation":[{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2162-400X","authenticated-orcid":false,"given":"An\u00edbal","family":"Mendez","sequence":"additional","affiliation":[{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6962-0676","authenticated-orcid":false,"given":"Edgar","family":"Portillo","sequence":"additional","affiliation":[{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8877-657X","authenticated-orcid":false,"given":"Mar\u00eda Elena","family":"Troconis","sequence":"additional","affiliation":[{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2426-779X","authenticated-orcid":false,"given":"Ariana","family":"Delgado","sequence":"additional","affiliation":[{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4300-6976","authenticated-orcid":true,"given":"Yasmir","family":"Quiroz","sequence":"additional","affiliation":[{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-2815","authenticated-orcid":false,"given":"Marylu","family":"Mora","sequence":"additional","affiliation":[{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2721-1142","authenticated-orcid":false,"given":"Yovani","family":"Marrero-Ponce","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda. 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