Abstract
BackgroundConstitutive 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.ResultsHere, 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.ConclusionsOur 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.
Highlights
Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes fine-tune responses to cues related to growth, development, and stresses
GEX1A inhibits plant growth and development and affects the splicing efficiency of a set of genes Very recently, we demonstrated that the macrolide pladienolide B (PB) causes global repression of pre-mRNA splicing [26]
All viable seeds germinated on control medium at 3 days after sowing (DAS), whereas less than 25% of seeds germinated on medium supplemented with 5 μM GEX1A
Summary
Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes fine-tune responses to cues related to growth, development, and stresses. Eukaryotes use transcriptional and post-transcriptional regulatory mechanisms to respond and adapt to their environment [1] Given their sessile nature and everchanging environmental conditions, plants exhibit strong plasticity at the epigenome and transcriptome levels to continuously adapt to a variety of growth and stress cues [1,2,3,4]. The splicing machinery recognizes cis-regulatory elements in the pre-mRNA, leading to the assembly or disassembly of spliceosome sub-complexes. Such cis-regulatory elements are key for spliceosome assembly and the recruitment of trans-acting factors that help it function [4, 5, 10, 11].
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