Pseudouridine (Ψ) is abundant in major classes of non-coding RNA (ncRNA), including ribosomal RNA, transfer RNA, and spliceosomal RNAs. The Watson-Crick base pairing potential of Ψ is identical to that of uridine, but Ψ may stabil...
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Descripción del proyecto
Pseudouridine (Ψ) is abundant in major classes of non-coding RNA (ncRNA), including ribosomal RNA, transfer RNA, and spliceosomal RNAs. The Watson-Crick base pairing potential of Ψ is identical to that of uridine, but Ψ may stabilize RNA structures and engage in RNA interactions distinct from those of uridine, probably explaining its requirement for cellular viability. In addition to the many constitutive Ψ-sites in major ncRNAs, recent reports have uncovered Ψ induced by specific stimuli or present in specific cell types, in rare cases with demonstrated importance for cellular translation and splicing patterns. Nonetheless, the full extent of occurrence and regulatory consequences of induced pseudouridylation remain unknown, highlighting the outstanding potential for discovery on this topic.
PSEUDOPIN builds on my observation that the gene encoding PseudoUridine Synthase PUS5 in the plant Arabidopsis thaliana exhibits mRNA isoform switching upon immune receptor activation: in growing seedlings, PUS5 encodes an organellar enzyme, but immune receptor activation induces transcription initiation at a downstream site to exclude the organellar target peptide from the PUS5 protein, thus giving rise to a nucleo-cytoplasmic enzyme. Two questions are being investigated here: (i) can we identify PUS5-dependent Ψ-sites upon immune receptor activation, and (ii) can we define functions of selected induced Ψ-sites in the growth-to-defense genetic reprogramming? PSEUDOPIN uses state-of-the-art sequencing methods, including direct RNA sequencing technology, to systematically map Ψ in major RNA classes after immune receptor stimulation. It also lays out strategies to select and study particularly interesting cases. The topic remains completely uninvestigated in plants, so the project promises to break open a new research field within plant gene expression, and thereby provide material to start an independent research career following successful completion of the fellowship.
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