Noncanoncial signal recognition particle RNAs in a major eukaryotic phylum revealed by purification of SRP from the human pathogen Cryptococcus neoformans.
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.
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
Phillip A
PA
Dumesic
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, SE-405 30, Sweden.
Magnus A
MA
Rosenblad
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, SE-405 30, Sweden.
Tore
T
Samuelsson
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
Tiffany
T
Nguyen
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
James J
JJ
Moresco
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
John R
JR
Yates
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA hitenmadhani@gmail.com.
Hiten D
HD
Madhani
D001487:Basidiomycota / Q000235:genetics; D003455:Cryptococcus neoformans / Q000235:genetics*; D005656:Fungal Proteins / Q000737:chemistry; D006801:Humans; D009690:Nucleic Acid Conformation; D017434:Protein Structure, Tertiary; D012331:RNA, Fungal / Q000737:chemistry* / Q000302:isolation & purification; D018271:Signal Recognition Particle / Q000737:chemistry* / Q000302:isolation & purification
D005656:Fungal Proteins; D012331:RNA, Fungal; D018271:Signal Recognition Particle