title: Herboxidiene triggers splicing repression and abiotic stress responses in plants.
abstract: Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes also fine-tune responses to cues related to growth, development, and stresses. Small-molecule inhibitors that perturb splicing provide invaluable tools for use as chemical probes to uncover the molecular underpinnings of splicing regulation and as potential anticancer compounds.
  
  
  
  Here, we show that herboxidiene (GEX1A) inhibits both constitutive and alternative splicing. Moreover, GEX1A activates genome-wide transcriptional patterns involved in abiotic stress responses in plants. GEX1A treatment -activated ABA-inducible promoters, and led to stomatal closure. Interestingly, GEX1A and pladienolide B (PB) elicited similar cellular changes, including alterations in the patterns of transcription and splicing, suggesting that these compounds might target the same spliceosome complex in plant cells.
  
  
  
  Our study establishes GEX1A as a potent splicing inhibitor in plants that can be used to probe the assembly, dynamics, and molecular functions of the spliceosome and to study the interplay between splicing stress and abiotic stresses, as well as having potential biotechnological applications.
authors.affiliation: Laboratory for Genome Engineering, Division of Biological Sciences, 4700 King Abdullah University of Science and Technology, Thuwal, 23955-6900, Saudi Arabia.
authors.forename: Sahar
authors.initials: S
authors.lastname: AlShareef
authors.affiliation: Laboratory for Genome Engineering, Division of Biological Sciences, 4700 King Abdullah University of Science and Technology, Thuwal, 23955-6900, Saudi Arabia.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Laboratory for Genome Engineering, Division of Biological Sciences, 4700 King Abdullah University of Science and Technology, Thuwal, 23955-6900, Saudi Arabia.
authors.forename: Haroon
authors.initials: H
authors.lastname: Butt
authors.affiliation: Laboratory for Genome Engineering, Division of Biological Sciences, 4700 King Abdullah University of Science and Technology, Thuwal, 23955-6900, Saudi Arabia.
authors.forename: Kiruthiga G
authors.initials: KG
authors.lastname: Mariappan
authors.affiliation: Laboratory for Genome Engineering, Division of Biological Sciences, 4700 King Abdullah University of Science and Technology, Thuwal, 23955-6900, Saudi Arabia.
authors.forename: Moussa
authors.initials: M
authors.lastname: Benhamed
authors.affiliation: Laboratory for Genome Engineering, Division of Biological Sciences, 4700 King Abdullah University of Science and Technology, Thuwal, 23955-6900, Saudi Arabia. magdy.mahfouz@kaust.edu.sa.
authors.forename: Magdy M
authors.initials: MM
authors.lastname: Mahfouz
mesh_terms: D000040:Abscisic Acid / Q000494:pharmacology; D017360:Arabidopsis / Q000235:genetics* / Q000254:growth & development; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D004852:Epoxy Compounds / Q000494:pharmacology; D005233:Fatty Alcohols / Q000494:pharmacology*; D018506:Gene Expression Regulation, Plant / Q000187:drug effects; D018525:Germination / Q000187:drug effects; D018942:Macrolides / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011714:Pyrans / Q000494:pharmacology*; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing / Q000187:drug effects*; D018749:RNA, Plant / Q000235:genetics / Q000378:metabolism*; D012639:Seeds / Q000254:growth & development; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects
chemical_list: D029681:Arabidopsis Proteins; D004852:Epoxy Compounds; D005233:Fatty Alcohols; D018942:Macrolides; D011714:Pyrans; D012322:RNA Precursors; D018749:RNA, Plant; C522342:pladienolide B; C076087:herboxidiene; D000068103:Serine-Arginine Splicing Factors; D000040:Abscisic Acid
keywords: ABA; Abiotic stress responses; Alternative splicing; GEX1A; Pladienolide B; SR proteins; Splicing inhibitors