Circularization of replication-dependent histone mRNAs during translation (2013)

Undergraduates: Jackson Trotman, Dr. Stacie Meaux, Dr. Bill Marzluff

Faculty Advisor: Bill Marzluff
Department: Chemistry

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Replication-dependent histone mRNAs have the distinction as the only observed eukaryotic mRNAs that do not end in a 3¿ poly-A tail; instead, they end in a 26-nucleotide stem-loop structure, which directly interacts with the stem-loop binding protein (SLBP). Accordingly, the cellular machinery required to process histone mRNAs is markedly different than that for other mRNAs. SLBP is centrally involved in all aspects of histone mRNA metabolism, and for SLBP to perform its multiple functions, it forms functional complexes with a multitude of other proteins, including the 80-kDa nuclear cap-binding protein (CBP80), which localizes to the 5¿ end of the mRNA. Refuting a previous study, I demonstrated that SLBP and CBP80 do not interact directly in vitro. Recent literature has suggested that a protein, CBP80/20-dependent translation initiation factor (CTIF), may serve as the bridge between SLBP and CBP80. CTIF has been shown to bind directly to CBP80, and here I show that it binds directly to SLBP as well as 3¿hEXO, another stem-loop interacting factor, and SLIP1, a factor known to be important for histone mRNA translation. My data show that SLBP and SLIP1 bind to CTIF at its N-terminal domain. It is well-reported that during translation, mRNAs containing poly-A tails circularize via protein-protein interactions. Our results shed light on the structural makeup of an analogous complex that may likewise circularize histone mRNAs to increase the efficiency of their translation.