{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T05:55:21Z","timestamp":1770270921195,"version":"3.49.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Plant Sci."],"abstract":"<jats:p>Copper (Cu) and iron (Fe) constitute fundamental nutrients for plant biology but are often limited due to low bioavailability. Unlike responses to single Cu or Fe deprivation, the consequences of simultaneous Cu and Fe deficiency have not yet been fully deciphered. Previously, it was demonstrated that Cu and Fe deficiency applied in combination imposes transcriptome, proteome, and metabolome changes different from those triggered under each deficiency individually. Here, we evaluated the effect of alternative splicing (AS) on the transcriptome of rosette leaves under single and simultaneous Cu and Fe deficiency. Differentially spliced genes (DSGs) and differentially expressed genes (DEGs) coincided in number (2,600 approx.) although the overlapping fraction was minimal (15%). Functional annotation of changes exclusively detected under simultaneous Cu and Fe deficiency revealed that DEGs participated in general stress responses and translation, while DSGs were involved in metabolic reactions, especially amino acid biosynthesis. Interestingly, transcripts encoding central features for tryptophan (Trp) and asparagine (Asn) synthesis \u2013 two significantly altered metabolites under simultaneous Cu and Fe deficiency \u2013 underwent exclusive intron retention events under the double deficiency. However, transcript and protein amounts for these enzymes did not correlate with Trp and Asn concentration. In consequence, we propose that AS might act as a regulatory mechanism to modify the stability and\/or functionality of the enzymes and therefore fine-tune amino acid production during the combinatorial response to simultaneous Cu and Fe deficiency.<\/jats:p>","DOI":"10.3389\/fpls.2022.827828","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T04:50:26Z","timestamp":1643604626000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Analysis of Alternative Splicing During the Combinatorial Response to Simultaneous Copper and Iron Deficiency in Arabidopsis Reveals Differential Events in Genes Involved in Amino Acid Metabolism"],"prefix":"10.3389","volume":"13","author":[{"given":"Estefania","family":"Mancini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoni","family":"Garcia-Molina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1105\/tpc.104.030452","article-title":"Two P-type ATPases are required for copper delivery in Arabidopsis thaliana chloroplasts.","volume":"17","author":"Abdel-Ghany","year":"2005","journal-title":"Plant Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1101\/gr.133744.111","article-title":"Detecting differential usage of exons from RNA-seq data.","volume":"22","author":"Anders","year":"2012","journal-title":"Genome Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2028","DOI":"10.1104\/pp.113.222372","article-title":"Identification of genes involved in the response of Arabidopsis to simultaneous biotic and abiotic stresses.","volume":"162","author":"Atkinson","year":"2013","journal-title":"Plant Physiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1105\/tpc.111.090431","article-title":"Transcriptome sequencing identifies SPL7-regulated copper acquisition genes FRO4\/FRO5 and the copper dependence of iron homeostasis in Arabidopsis.","volume":"24","author":"Bernal","year":"2012","journal-title":"Plant Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1105\/tpc.18.00177","article-title":"Rapid and dynamic alternative splicing impacts the Arabidopsis cold response transcriptome.","volume":"30","author":"Calixto","year":"2018","journal-title":"Plant Cell"},{"key":"B6","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.tplants.2019.02.006","article-title":"Perspective on alternative splicing and proteome complexity in plants.","volume":"24","author":"Chaudhary","year":"2019","journal-title":"Trends Plant Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3400","DOI":"10.1105\/tpc.104.024315","article-title":"The essential basic helix-loop-helix protein FIT1 is required for the iron deficiency response.","volume":"16","author":"Colangelo","year":"2004","journal-title":"Plant Cell"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification.","volume":"26","author":"Cox","year":"2008","journal-title":"Nat. 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