Global mRNA selection mechanisms for translation initiation

摘要

Background: The selection and regulation of individual m RNAs for translation initiation from a competing pool of m RNA are poorly understood processes. The closed loop complex, comprising e IF4E, e IF4G and PABP, and its regulation by 4E-BPs are perceived to be key players. Using RIP-seq, we aimed to evaluate the role in gene regulation of the closed loop complex and 4E-BP regulation across the entire yeast transcriptome. Results: We find that there are distinct populations of m RNAs with coherent properties: one m RNA pool contains many ribosomal protein m RNAs and is enriched specifically with all of the closed loop translation initiation components. This class likely represents m RNAs that rely heavily on the closed loop complex for protein synthesis. Other heavily translated m RNAs are apparently under-represented with most closed loop components except Pab1p. Combined with data showing a close correlation between Pab1p interaction and levels of translation, these data suggest that Pab1p is important for the translation of these m RNAs in a closed loop independent manner. We also identify a translational regulatory mechanism for the 4E-BPs; these appear to self-regulate by inhibiting translation initiation of their own m RNAs. Conclusions: Overall, we show that m RNA selection for translation initiation is not as uniformly regimented as previously anticipated. Components of the closed loop complex are highly relevant for many m RNAs, but some heavily translated m RNAs interact poorly with this machinery. Therefore, alternative, possibly Pab1p-dependent mechanisms likely exist to load ribosomes effectively onto m RNAs. Finally, these studies identify and characterize a complex self-regulatory circuit for the yeast 4E-BPs.