Short and Sweet: Viral 5`-UTR as a Canonical and Non-Canonical Translation Initiation Switch

Abstract

Canonical translation initiation is a complex, multistep process that requires coordinated activity of multiple translation initiation factors (eIFs). It begins when the methyl-7-guanosine (m7G) structure is co-translationally

A novel reporter for helicase activity in translation uncovers DDX3X interactions

“…Notably, the TISU function does not require eIF4A, suggesting that some short 5′ UTRs lack the need for DEAD-box helicases ( Sinvani et al 2015 ). Similarly, cap-assisted translation without scanning was reported for the histone H4 mRNA, which is notable for directing translation in a wide variety of eukaryotic cells ( Dasmahapatra et al 1987 ; Martin et al 2011 ; Trainor and Shcherbik 2021 ). It is possible that this extremely short 5′ UTR avoids DDX3X dependency by initiating translation without ribosome scanning or by cap-independent mechanisms altogether, hence without the need for the unwinding of complex structures.…”

“…In addition to its lack of complex RNA structure, there could be other reasons that make it insensitive to permutations in DDX3X. Very short 5′ UTRs promote translation in cap-dependent and -independent mechanisms ( Trainor and Shcherbik 2021 ). Additionally, even in the context of cap-dependent translation, they have been observed to direct translation in a ribosome scanning–free manner ( Elfakess et al 2011 ; Haimov et al 2015 ).…”

In Vitro Transcribed RNA-Based Platform Vaccines: Past, Present, and Future

“…These IRESs structurally mimic Met-tRNAi. Cricket paralysis virus (CrPV) and Taura syndrome virus (TSV) are prominent examples of Class IV IRESs [50][51][52][53]. It is noteworthy that viral IRESs incorporated into IVT mRNAs have demonstrated higher protein production levels compared to cellular IRESs such as eukaryotic initiation factor 4G (eIF4G), fragile X Messenger Ribonucleoprotein 1 (FMR1), or connexin 43 (CN43) [50].…”

Recruitment of the 40S ribosomal subunit by the West Nile virus 3′ UTR promotes the cross-talk between the viral genomic ends for translation regulation

“…During early infection, single-stranded positive RNA viruses make use of the translational cellular machinery to synthesize viral proteins ( Firth and Brierley, 2012 ; Reineke and Lloyd, 2011 ). The sequestration and management of this machinery is accomplished by highly structured RNA elements especially accumulated at both ends of the viral RNA genome, but also dispersed throughout it ( Firth and Brierley, 2012 ; Trainor and Shcherbik, 2021 ). In flaviviruses, these elements coordinate a translation mechanism that differs from the canonical cap-dependent one, thus contributing to the evasion of the cellular defense systems by the virus ( Jaafar and Kieft, 2019 ; Sorokin et al, 2021 ).…”