The study investigates the role of N6-methyladenosine (m6A) mRNA methylation in the heat shock response. It is found that m6A is preferentially deposited in the 5' untranslated region (5'UTR) of newly transcribed mRNAs in response to heat shock stress. This dynamic 5'UTR methylation is regulated by the nuclear localization of YTHDF2, a well-characterized m6A "reader," which limits the activity of the m6A "eraser" FTO. The increased 5'UTR methylation promotes cap-independent translation initiation, providing a mechanism for selective mRNA translation under heat shock stress. Using Hsp70 mRNA as an example, the study demonstrates that a single site m6A modification in the 5'UTR enables cap-independent translation initiation. The findings expand the understanding of m6A's physiological roles and uncover a novel translational control mechanism in the heat shock response.The study investigates the role of N6-methyladenosine (m6A) mRNA methylation in the heat shock response. It is found that m6A is preferentially deposited in the 5' untranslated region (5'UTR) of newly transcribed mRNAs in response to heat shock stress. This dynamic 5'UTR methylation is regulated by the nuclear localization of YTHDF2, a well-characterized m6A "reader," which limits the activity of the m6A "eraser" FTO. The increased 5'UTR methylation promotes cap-independent translation initiation, providing a mechanism for selective mRNA translation under heat shock stress. Using Hsp70 mRNA as an example, the study demonstrates that a single site m6A modification in the 5'UTR enables cap-independent translation initiation. The findings expand the understanding of m6A's physiological roles and uncover a novel translational control mechanism in the heat shock response.