ena-STUDY-TECHNION - ISAEL INSTITUTE IF TECHNOLOGY-24-01-2019-15:22:45:385-1202
mRNA association by aminoacyl tRNA synthetase occurs at an anticodon mimic and autoregulates translation in response to tRNA levels
Aminoacyl tRNA synthetases (aaRSs) are well-studied for their role in binding andcharging tRNAs with cognate amino acids. Recent RNA interactome studies hadsuggested that these enzymes can also bind polyadenylated RNAs. Here we exploredthe mRNA repertoire bound by several yeast aaRSs. RNA-immunoprecipitationfollowed by deep sequencing revealed unique sets of mRNAs bound by each aaRS.Interestingly, for every tested aaRSs, a preferential association with its own mRNA wasobserved, suggesting an autoregulatory process. Self-association of histidylsynthetase(HisRS) was found to be mediated primarily through binding to a tRNAHisanticodon-like structure. Point mutation within this anticodon-mimic alleviated selfassociation,concomitant with increased synthesis of the protein. Finally, we found thatincreased cellular levels of uncharged tRNAHis lead to reduced self-association andincreased HisRS translation, in a manner that depends on the anticodon mimic.Together, these results reveal a novel post-transcriptional auto-regulatory mechanismthat exploits binding mimicry to control mRNA translation according to tRNA demands
Aminoacyl tRNA synthetases (aaRSs) are well-studied for their role in binding andcharging tRNAs with cognate amino acids. Recent RNA interactome studies hadsuggested that these enzymes can also bind polyadenylated RNAs. Here we exploredthe mRNA repertoire bound by several yeast aaRSs. RNA-immunoprecipitationfollowed by deep sequencing revealed unique sets of mRNAs bound by each aaRS.Interestingly, for every tested aaRSs, a preferential association with its own mRNA wasobserved, suggesting an autoregulatory process. Self-association of histidylsynthetase(HisRS) was found to be mediated primarily through binding to a tRNAHisanticodon-like structure. Point mutation within this anticodon-mimic alleviated selfassociation,concomitant with increased synthesis of the protein. Finally, we found thatincreased cellular levels of uncharged tRNAHis lead to reduced self-association andincreased HisRS translation, in a manner that depends on the anticodon mimic.Together, these results reveal a novel post-transcriptional auto-regulatory mechanismthat exploits binding mimicry to control mRNA translation according to tRNA demands