A Translation Initiation Element Specific to mRNAs with Very Short 5′UTR that Also Regulates Transcription

Transcription is controlled by cis regulatory elements, which if localized downstream to the transcriptional start site (TSS), in the 5′UTR, could influence translation as well. However presently there is little evidence for such composite regulatory elements. We have identified by computational analysis an abundant element located downstream to the TSS up to position +30, which controls both transcription and translation. This element has an invariable ATG sequence, which serves as the translation initiation codon in 64% of the genes bearing it. In these genes the initiating AUG is preceded by an extremely short 5′UTR. We show that translation in vitro and in vivo is initiated exclusively from the AUG of this motif, and that the AUG flanking sequences create a strong translation initiation context. This motif is distinguished from the well-known Kozak in its unique ability to direct efficient and accurate translation initiation from mRNAs with a very short 5′UTR. We therefore named it TISU for Translation Initiator of Short 5′UTR. Interestingly, this translation initiation element is also an essential transcription regulatory element of Yin Yang 1. Our characterization of a common transcription and translation element points to a link between mammalian transcription and translation initiation.