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This chapter discusses the question of coping up of the nucleic acids with high temperature at the polynucleotide level—RNA, DNA, and their ribonucleoprotein derivatives (RNP/DNP). When nucleic acids are heated in aqueous solution, two types of phenomena take place: denaturation of their architecture and chemical degradation of their building blocks. In vivo, the half-lives of both RNA and DNA of thermophilic organisms are usually longer than that estimated in vitro, attesting to cellular strategies protecting the nucleic acids against the deleterious effects of heat. Despite the susceptibility of certain modified bases and of the ribonucleotide chain to thermal degradation, most naturally occurring tRNAs (especially those from hyperthermophilic organisms) appear fairly resistant to heat denaturation. Despite the intrinsic potentiality of nucleic acids to degrade at elevated temperatures, many hyperthermophiles can survive at very high temperatures approaching or even surpassing the boiling point of water. The majority of stable cellular RNAs, such as tRNA and rRNA molecules, contain a variety of modified nucleosides. Stabilizing strategies of RNAs and DNAs may be classified into three major categories: (i) those which are intrinsic to the chemical structures of the nucleic acids; (ii) those which are dependent on extrinsic interactions with other biomolecules; and (iii) those which are dependent on a battery of enzymes for detecting and repairing the DNA damage or to constantly renew functional RNA molecules. Genetic approach using mutant strains mutated in one or more biomolecules supposedly involved directly or indirectly in stabilization of nucleic acids should be more systematically used.