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Structural basis for sequence-nonspecific recognition of 5'-capped mRNA by a cap-modifying enzyme
A E Hodel1, P D Gershon, F A Quiocho
1Howard Hughes Medical Institute, Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA.
Molecular Cell
|July 14, 1998
Summary
Researchers reveal the crystal structure of a methyltransferase complex, showing how it recognizes capped mRNA by binding its sugar-phosphate backbone, not specific sequences.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Eukaryotic nucleic acid processing involves sequence-nonspecific RNA binding, 7-methylguanosine (m7G) mRNA cap recognition, and nucleic acid backbone methylation.
- The vaccinia virus methyltransferase VP39 performs these three crucial events concurrently during mRNA modification.
Purpose of the Study:
- To elucidate the structural mechanism of concurrent RNA binding, cap recognition, and methylation by VP39.
- To provide the first detailed structural view of a protein complexed with single-stranded RNA and a 5'-capped mRNA.
Main Methods:
- X-ray crystallography was used to determine the structure of a ternary complex.
- The complex included the methyltransferase VP39, the coenzyme product S-adenosylhomocysteine, and a 5' m7G-capped single-stranded RNA hexamer.
Main Results:
- The crystal structure reveals a novel mechanism for sequence-non-specific mRNA recognition.
- VP39 interacts exclusively with the sugar-phosphate backbone of the single-stranded RNA.
- The structure captures the protein in the act of modifying a capped mRNA transcript.
Conclusions:
- The findings present a general mechanism for how proteins can recognize mRNA transcripts without binding to specific sequences.
- This structural insight is critical for understanding eukaryotic mRNA processing and function.
- The study offers the first direct structural evidence of protein interaction with single-stranded, 5'-capped mRNA.