Transcription and translation in a package deal: The TISU paradigm

The major strategy for cap dependent translation involves ribosomal scanning. In the scanning mechanism the small ribosomal subunit is recruited to the mRNA through the m7G cap and then scans the 5′ UTR until it reaches an AUG codon. This short review focuses on a recently discovered alternative strategy of cap-dependent translation that operates without scanning, but nonetheless is highly efficient and accurate. This non-scanning translation is directed by the Translation Initiator of Short 5′ UTR (TISU) element. TISU is strictly located close to the 5′ end of the mRNA, resulting in a very short 5′ UTR. It is present in a sizable number of mammalian genes, many of them with fundamental cellular functions. In addition to its unique translational activity, TISU is also a transcription regulatory element that is specifically enriched in TATA-less promoters. Thus TISU represents a prototype regulatory element that links mammalian transcription to a specific mode of translation initiation.