Ionizing radiation and chemical oxidant exposure impacts on Cryptococcus neoformans transfer RNAs

Abstract

Cryptococcus neoformansis a fungus that is able to survive abnormally high levels of ionizing radiation (IR). The radiolysis of water by IR generates reactive oxygen species (ROS) such as H2O2and OH-.C.neoformanswithstands the damage caused by IR and ROS through antioxidant production and enzyme-catalyzed breakdown of ROS. Given these particular cellular protein needs, questions arise whether transfer ribonucleic acids molecules (tRNAs) undergo unique chemical modifications to maintain their structure, stability, and/or function under such environmental conditions. Here, we investigated the effects of IR and H2O2exposure on tRNAs inC.neoformans. We experimentally identified the modified nucleosides present inC.neoformanstRNAs and quantified changes in those modifications upon exposure to oxidative conditions. To better understand these modified nucleoside results, we also evaluated tRNA pool composition in response to the oxidative conditions. We found that regardless of environmental conditions, tRNA modifications and transcripts were minimally affected. A rationale for the stability of the tRNA pool and its concomitant profile of modified nucleosides is proposed based on the lack of codon bias throughout theC.neoformansgenome and in particular for oxidative response transcripts. Our findings suggest thatC.neoformanscan rapidly adapt to oxidative environments as mRNA translation/protein synthesis are minimally impacted by codon bias.

Document Details

Document Type
Pub Defense Publication
Publication Date
Mar 29, 2022
Source ID
10.1371/journal.pone.0266239

Entities

People

  • Balasubrahmanyam Addepalli
  • George Yoshida
  • Joel P. Levoy
  • Joshua B. Benoit
  • Manasses Jora
  • Melissa Kelley
  • Mellie June Paulines
  • Patrick A. Limbach
  • Ryan Myers

Organizations

  • Defense Threat Reduction Agency
  • Division of Chemistry

Tags

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Organic Chemistry
  • Systems Analysis and Design