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Modeling the Structure and Function of Argonaute in RNAi
Author(s) -
Clark Philip,
Cohen Matthew,
Danziger Sunaina,
Eisner Lauren,
HerzRoiphe Rachel,
Iwahara Yuri,
Kafka Oliver,
Kiprovski Aleksandar,
Koones Gabrielle,
Milich Andrew,
Mittal Sonia,
Richardson Alia,
Rubenstein Jordan,
Shapiro Jack,
Stern Alexandra,
Zhao Yinge,
Hackett Jennifer,
JoshuaTor Leemor
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb188
Subject(s) - argonaute , rna interference , rna induced silencing complex , small interfering rna , trans acting sirna , gene silencing , microbiology and biotechnology , rna silencing , biology , messenger rna , rna , gene , genetics
RNA Interference (RNAi) regulates gene expression in almost all eukaryotic cells by degrading specific mRNA molecules. A key step in this process is the cleavage of mRNA molecules by the endonuclease Argonaute. The Dalton School SMART Team (Students Modeling A Research Topic) modeled the structure and function of the Argonaute protein using 3D printing technology. RNAi specifically degrades mRNA molecules that are complementary to short interfering RNA (siRNA) molecules. Cells produce siRNAs from double‐stranded RNA molecules that could be made by viruses or that could be transcribed from the cell's own regulatory genes. Argonaute binds an siRNA molecule, forming the RNA‐induced silencing complex (RISC). The siRNA in RISC binds a complementary mRNA, allowing Argonaute to cut the mRNA in the middle, which is then degraded by exonucleases. Argonaute is composed of four domains. Three of the domains form a crescent‐shaped base that includes the active site at the center of the base. A positively‐charged cleft between this base and the fourth domain holds the negatively‐charged siRNA. The siRNA binds to a complementary mRNA, positioning it so that aspartic acid residues in the active site can slice the mRNA into two fragments, thus preventing translation of the mRNA. Strategies that use RNAi to treat disease are currently in development. Supported by a grant from the Camille and Henry Dreyfus Foundation.