Translation is essential for all biological processes including development, differentiation, growth, cell fitness and cellular adaptive responses to the external environment. Consequently, regulatory dysfunction in translation is associated with various human diseases such as metabolic disorders, neuronal degenerative diseases and cancer. Our long-term goal is to elucidate molecular mechanisms of translation and translational control in gene expression, and to understand how errors in this process are related to human disease. Towards this goal, the overall objective of the proposed research is to elucidate molecular mechanisms and interactions that enable RNA-binding protein Sbp1 to remodel and activate the 5' untranslated regions (5'UTRs) of mRNAs encoding eukaryotic initiation factor 4G (eIF4G). Four independent but complementary aims are proposed.
Aim 1 pursues a molecular understanding of how Sbp1 influences the formation of intermediates in translation initiation of the eIF4G mRNAs.
Aim 2 and 3 seek to understand the functions of individual domains of the Sbp1 in modulating protein- protein and protein-RNA interactions.
Aim 4 is designed to reveal molecular architectures of several functional 5'UTR-protein complexes in translation initiation.
These aims will be accomplished by using biochemical methods.
Translation is a fundamental biological process in all living cells: comprehension of the fundamental principles governing translation will lead to an understanding of how its dys- regulation is associated with human disease, and provide new treatment strategies in medicine. Aberrant regulation of the translation machinery and its components is a defining characteristic of all cancer cell-lines, and translation of the initiation factor eIF4G is drastically up-regulated in nasopharyngeal carcinoma, lung and breast cancers. A better understanding of the regulatory potential of the 5'UTRs of eIF4G by RNA-binding proteins may provide new approaches for treating these cancers.
|Zeng, Fuxing; Jin, Hong (2018) Conformation of methylated GGQ in the Peptidyl Transferase Center during Translation Termination. Sci Rep 8:2349|
|Brandariz-Núñez, Alberto; Zeng, Fuxing; Lam, Quan Ngoc et al. (2018) Sbp1 modulates the translation of Pab1 mRNA in a poly(A)- and RGG-dependent manner. RNA 24:43-55|
|Zeng, Fuxing; Chen, Yanbo; Remis, Jonathan et al. (2017) Structural basis of co-translational quality control by ArfA and RF2 bound to ribosome. Nature 541:554-557|