MRNA 5' terminal sequences drive 200-fold differences in expression through effects on synthesis, translation and decay.

ABSTRACT: mRNA regulatory sequences control gene expression at multiple levels including translation initiation and mRNA decay. The 5' terminal sequences of mRNAs have unique regulatory potential because of their proximity to key post-transcriptional regulators. Here we have systematically probed the function of 5' terminal sequences in gene expression in human cells. Using a library of reporter mRNAs initiating with all possible 7-mer sequences at their 5' ends, we find an unexpected impact on transcription that underlies 200-fold differences in mRNA expression. Library sequences that promote high levels of transcription mirrored those found in native mRNAs and define two basic classes with similarities to classic Initiator (Inr) and TCT core promoter motifs. By comparing transcription, translation

SUBMITTER: van den Elzen AMG 

PROVIDER: S-EPMC9731452 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature