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Noncanoncial signal recognition particle RNAs in a major eukaryotic phylum revealed by purification of SRP from the human pathogen Cryptococcus neoformans.

Artikel i vetenskaplig tidskrift
Författare Phillip A Dumesic
Magnus Alm Rosenblad
Tore Samuelsson
Tiffany Nguyen
James J Moresco
John R Yates
Hiten D Madhani
Publicerad i Nucleic acids research
Volym 43
Nummer/häfte 18
Sidor 9017-9027
ISSN 1362-4962
Publiceringsår 2015
Publicerad vid Institutionen för kemi och molekylärbiologi
Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Sidor 9017-9027
Språk en
Länkar dx.doi.org/10.1093/nar/gkv819
Ämnesord srp, rna, bioinformatik, basidiomycota
Ämneskategorier Bioinformatik och systembiologi

Sammanfattning

Despite conservation of the signal recognition particle (SRP) from bacteria to man, computational approaches have failed to identify SRP components from genomes of many lower eukaryotes, raising the possibility that they have been lost or altered in those lineages. We report purification and analysis of SRP in the human pathogen Cryptococcus neoformans, providing the first description of SRP in basidiomycetous yeast. The C. neoformans SRP RNA displays a predicted structure in which the universally conserved helix 8 contains an unprecedented stem-loop insertion. Guided by this sequence, we computationally identified 152 SRP RNAs throughout the phylum Basidiomycota. This analysis revealed additional helix 8 alterations including single and double stem-loop insertions as well as loop diminutions affecting RNA structural elements that are otherwise conserved from bacteria to man. Strikingly, these SRP RNA features in Basidiomycota are accompanied by phylum-specific alterations in the RNA-binding domain of Srp54, the SRP protein subunit that directly interacts with helix 8. Our findings reveal unexpected fungal SRP diversity and suggest coevolution of the two most conserved SRP features-SRP RNA helix 8 and Srp54-in basidiomycetes. Because members of this phylum include important human and plant pathogens, these noncanonical features provide new targets for antifungal compound development.

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