EMBO Conference on Protein Synthesis and Translational Control

RIVKA DIKSTEIN
Characterization of TISU, a translation initiator specific to mRNAs with
extremely short 5’UTR
Weizmann Institute of Science, Israel
9
Speaker Abstracts
Regulation of expression of protein-encoding gene occurs primarily at the initiation stage of
transcription and translation. Transcription is controlled by regulatory elements, proximal and
distal to the transcription start site (TSS). Some proximal elements are localized downstream to
the TSS, and are present in the mRNA as well, often in the 5’UTR, where they could also
influence translation. However there is little evidence for the existence of such common
transcription and translation regulatory elements. We have identified an element downstream
to the TSS up to position +30, which, remarkably, controls the initiation stages of both
transcription and translation. This composite element is present in genes encoding for proteins
involved in basic cellular functions such as respiration, protein metabolism and RNA synthesis.
We showed this element to be essential for transcription initiation and promoter strength. The
core of the motif has an invariable ATG sequence, which serves also as the translation initiation
codon in the majority of the genes. In these genes the initiating AUG is preceded by an
unusually short 5’UTR. We demonstrated 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 that 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
without ribosome scanning. We therefore named it TISU for Translation Initiator of Short
5’UTR. Our findings suggest that the transcription and translation processes, once considered
to be independent of each other due to cellular compartmentalization, are linked through a
common regulatory element.