title: Alternative splicing mechanisms orchestrating post-transcriptional gene expression: intron retention and the intron-rich genome of apicomplexan parasites.
abstract: Apicomplexan parasites including Toxoplasma gondii and Plasmodium species have complex life cycles that include multiple hosts and differentiation through several morphologically distinct stages requiring marked changes in gene expression. This review highlights emerging evidence implicating regulation of mRNA splicing as a mechanism to prime these parasites for rapid gene expression upon differentiation. We summarize the most important insights in alternative splicing including its role in regulating gene expression by decreasing mRNA abundance via 'Regulated Unproductive Splicing and Translation'. As a related but less well-understood mechanism, we discuss also our recent work suggesting a role for intron retention for precluding translation of stage specific isoforms of T. gondii glycolytic enzymes. We additionally provide new evidence that intron retention might be a widespread mechanism during parasite differentiation. Supporting this notion, recent genome-wide analysis of Toxoplasma and Plasmodium suggests intron retention is more pervasive than heretofore thought. These findings parallel recent emergence of intron retention being more prevalent in mammals than previously believed, thereby adding to the established roles in plants, fungi and unicellular eukaryotes. Deeper mechanistic studies of intron retention will provide important insight into its role in regulating gene expression in apicomplexan parasites and more general in eukaryotic organisms.
authors.affiliation: Department of Chemistry, Biology and Biotechnology, University of Perugia, via del Giochetto, 06122, Perugia, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lunghi
authors.affiliation: Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Furio
authors.initials: F
authors.lastname: Spano
authors.affiliation: Department of Chemistry, Biology and Biotechnology, University of Perugia, via del Giochetto, 06122, Perugia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Magini
authors.affiliation: Department of Chemistry, Biology and Biotechnology, University of Perugia, via del Giochetto, 06122, Perugia, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Emiliani
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Vern B
authors.initials: VB
authors.lastname: Carruthers
authors.affiliation: Department of Chemistry, Biology and Biotechnology, University of Perugia, via del Giochetto, 06122, Perugia, Italy. manlio.dicristina@unipg.it.
authors.forename: Manlio
authors.initials: M
authors.lastname: Di Cristina
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D007438:Introns; D010271:Parasites / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D020543:Proteome; D012323:RNA Processing, Post-Transcriptional; D014122:Toxoplasma / Q000235:genetics / Q000378:metabolism
chemical_list: D020543:Proteome
keywords: Alternative splicing; Apicomplexan parasites; Intron retention; Plasmodium falciparum; Toxoplasma gondii