Autoselection of Cytoplasmic Yeast Virus Like Elements Encoding Toxin/Antitoxin Systems Involves a Nuclear Barrier for Immunity Gene Expression

Cytoplasmic virus like elements (VLEs) from Kluyveromyces lactis (Kl), Pichia acaciae (Pa) and Debaryomyces robertsiae (Dr) are extremely A/T-rich (>75%) and encode toxic anticodon nucleases (ACNases) along with specific immunity proteins. Here we show that nuclear, not cytoplasmic expression of...

Verfasser: Kast, Alene
Voges, Raphael
Schroth, Michael
Schaffrath, Raffael
Klassen, Roland
Meinhardt, Friedhelm
Dokumenttypen:Artikel
Medientypen:Text
Erscheinungsdatum:2015
Publikation in MIAMI:01.06.2015
Datum der letzten Änderung:27.01.2023
Angaben zur Ausgabe:[Electronic ed.]
Quelle:PLOS Genetics 11 (2015) 5, e1005005, 1-17
Fachgebiet (DDC):570: Biowissenschaften; Biologie
Lizenz:CC BY 4.0
Sprache:English
Anmerkungen:Finanziert durch den Open-Access-Publikationsfonds 2014/2015 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF-Dokument
ISSN:1553-7404
URN:urn:nbn:de:hbz:6-69249717011
Weitere Identifikatoren:DOI: doi:10.1371/journal.pgen.1005005
Permalink:https://nbn-resolving.de/urn:nbn:de:hbz:6-69249717011
Onlinezugriff:journal.pgen.1005005.pdf

Cytoplasmic virus like elements (VLEs) from Kluyveromyces lactis (Kl), Pichia acaciae (Pa) and Debaryomyces robertsiae (Dr) are extremely A/T-rich (>75%) and encode toxic anticodon nucleases (ACNases) along with specific immunity proteins. Here we show that nuclear, not cytoplasmic expression of either immunity gene (PaORF4, KlORF3 or DrORF5) results in transcript fragmentation and is insufficient to establish immunity to the cognate ACNase. Since rapid amplification of 3' ends (RACE) as well as linker ligation of immunity transcripts expressed in the nucleus revealed polyadenylation to occur along with fragmentation, ORF-internal poly(A) site cleavage due to the high A/T content is likely to prevent functional expression of the immunity genes. Consistently, lowering the A/T content of PaORF4 to 55% and KlORF3 to 46% by gene synthesis entirely prevented transcript cleavage and permitted functional nuclear expression leading to full immunity against the respective ACNase toxin. Consistent with a specific adaptation of the immunity proteins to the cognate ACNases, cross-immunity to non-cognate ACNases is neither conferred by PaOrf4 nor KlOrf3. Thus, the high A/T content of cytoplasmic VLEs minimizes the potential of functional nuclear recruitment of VLE encoded genes, in particular those involved in autoselection of the VLEs via a toxin/antitoxin principle.