TY - JOUR
T1 - Crystal Structures of T. brucei MRP1/MRP2 Guide-RNA Binding Complex Reveal RNA Matchmaking Mechanism
AU - Schumacher, Maria A.
AU - Karamooz, Elham
AU - Zíková, Alena
AU - Trantírek, Lukáš
AU - Lukeš, Julius
N1 - Funding Information:
This work was supported by the Burroughs Wellcome Career Development Award 992863 and MD Anderson Research Trust Fellowship (to M.A.S), National Institutes of Health grant 5R03TW6445 (to Ken Stuart and J.L.), and Grant Agency of the Czech Republic grant P191/2004 (to L.T.).
PY - 2006/8/25
Y1 - 2006/8/25
N2 - The mitochondrial RNA binding proteins MRP1 and MRP2 form a heteromeric complex that functions in kinetoplastid RNA editing. In this process, MRP1/MRP2 serves as a matchmaker by binding to guide RNAs and facilitating their hybridization with cognate preedited mRNAs. To understand the mechanism by which this complex performs RNA matchmaking, we determined structures of Trypanosoma brucei apoMRP1/MRP2 and an MRP1/MRP2-gRNA complex. The structures show that MRP1/MRP2 is a heterotetramer and, despite little sequence homology, each MRP subunit exhibits the same "Whirly" transcription-factor fold. The gRNA molecule binds to the highly basic β sheet surface of the MRP complex via nonspecific, electrostatic contacts. Strikingly, while the gRNA stem/loop II base is anchored to the basic surface, stem/loop I (the anchor sequence) is unfolded and its bases exposed to solvent. Thus, MRP1/MRP2 acts as an RNA matchmaker by stabilizing the RNA molecule in an unfolded conformation suitable for RNA-RNA hybridization.
AB - The mitochondrial RNA binding proteins MRP1 and MRP2 form a heteromeric complex that functions in kinetoplastid RNA editing. In this process, MRP1/MRP2 serves as a matchmaker by binding to guide RNAs and facilitating their hybridization with cognate preedited mRNAs. To understand the mechanism by which this complex performs RNA matchmaking, we determined structures of Trypanosoma brucei apoMRP1/MRP2 and an MRP1/MRP2-gRNA complex. The structures show that MRP1/MRP2 is a heterotetramer and, despite little sequence homology, each MRP subunit exhibits the same "Whirly" transcription-factor fold. The gRNA molecule binds to the highly basic β sheet surface of the MRP complex via nonspecific, electrostatic contacts. Strikingly, while the gRNA stem/loop II base is anchored to the basic surface, stem/loop I (the anchor sequence) is unfolded and its bases exposed to solvent. Thus, MRP1/MRP2 acts as an RNA matchmaker by stabilizing the RNA molecule in an unfolded conformation suitable for RNA-RNA hybridization.
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U2 - 10.1016/j.cell.2006.06.047
DO - 10.1016/j.cell.2006.06.047
M3 - Article
C2 - 16923390
AN - SCOPUS:33747478692
SN - 0092-8674
VL - 126
SP - 701
EP - 711
JO - Cell
JF - Cell
IS - 4
ER -