Post-transcriptional methylation of N6-adenine and Nl-adenine can affect transcriptome turnover and translation.Furthermore,the regulatory function of N6-methyladenine(m6A)during heat shock has been uncovered,includin...Post-transcriptional methylation of N6-adenine and Nl-adenine can affect transcriptome turnover and translation.Furthermore,the regulatory function of N6-methyladenine(m6A)during heat shock has been uncovered,including the enhancement of the phase separation potential of RNAs.In response to acute stress,e.g.heat shock,the orderly sequestration of mRNAs in stress granules(SGs)is considered important to protect transcripts from the irreversible aggregation.Until recently,the role of N1-methyladenine(m^(1)A)on mRNAs during acute stress response remains largely unknown.Here we show that the methyltransferase complex TRMT6/61A,which generates the tag,is involved in transcriptome protection during heat shock.Our bioinformatics analysis indicates that occurrence of the motif is increased in mRNAs known to be enriched in SGs.Accordingly,the m^(1)A-generating methyltransferase TRMT6/61A accumulated in SGs and mass spectrometry confirmed enrichment of in the SG RNAs.The insertion of a single methylation motif in the untranslated region of a reporter RNA leads to more efficient recovery of protein synthesis from that transcript after the return to normal temperature.Our results demonstrate far-reaching functional consequences of a minimal RNA modification on N1-adenine during acute proteostasis stress.展开更多
基金This work was funded by the European Research Council grants MetaMeta_311522(R.M.V.)RIBOMYLOME_309545(G.G.T.)+5 种基金ASTRA_855923(G.G.T)G.G.T.acknowledges support of the H2020 projects IASIS_727658 and INFORE_825080the Spanish Ministry of Economy and Competitiveness BFU2017-86970-Pas well as the collaboration with Peter St.George-Hyslop financed by the Wellcome TrustR.M.V.acknowledges support by the Deutsche Forschungsgemeinschaft(DFG)grant EXC115M.H.is funded by DFG CRC902‘Molecular Principles of RNA-based Regulation’。
文摘Post-transcriptional methylation of N6-adenine and Nl-adenine can affect transcriptome turnover and translation.Furthermore,the regulatory function of N6-methyladenine(m6A)during heat shock has been uncovered,including the enhancement of the phase separation potential of RNAs.In response to acute stress,e.g.heat shock,the orderly sequestration of mRNAs in stress granules(SGs)is considered important to protect transcripts from the irreversible aggregation.Until recently,the role of N1-methyladenine(m^(1)A)on mRNAs during acute stress response remains largely unknown.Here we show that the methyltransferase complex TRMT6/61A,which generates the tag,is involved in transcriptome protection during heat shock.Our bioinformatics analysis indicates that occurrence of the motif is increased in mRNAs known to be enriched in SGs.Accordingly,the m^(1)A-generating methyltransferase TRMT6/61A accumulated in SGs and mass spectrometry confirmed enrichment of in the SG RNAs.The insertion of a single methylation motif in the untranslated region of a reporter RNA leads to more efficient recovery of protein synthesis from that transcript after the return to normal temperature.Our results demonstrate far-reaching functional consequences of a minimal RNA modification on N1-adenine during acute proteostasis stress.
