| HRA003861
(Controlled Access)
|
Although most eukaryotic mRNAs require the 5'-cap for translation, some mRNAs can also be translated through a cap-independent pathway. Here we developed a cell-based system to unbiasedly screen human transcriptome for sequences that drive cap-independent circRNA translation, and identified more than 10,000 endogenous sequences. These sites were found in all mRNA regions, with features distinct from canonical IRESs, and thus were defined as Cap-independent Translation Initiation sites (CiTI). The CiTIs at 5'-UTR tend to pair with 18S rRNA to promote translation. However, the CiTIs at 3'-UTR may function either as IRESs to drive downstream ORF translation, or as translation enhancers to promote upstream main ORF translation by unwinding the highly structured 5'-UTR. We further identified trans-acting factors that specifically bind CiTIs at 3'-UTR to promote upstream ORF translation, including several components of translation initiation complexes such as DHX29. |
