Structural basis for telomerase RNA recognition and RNP assembly by the holoenzyme La family protein p65.
Telomerase is a ribonucleoprotein complex essential for maintenance of telomere DNA at linear chromosome ends. The catalytic core of Tetrahymena telomerase comprises a ternary complex of telomerase RNA (TER), telomerase reverse transcriptase (TERT), and the essential La family protein p65. NMR and crystal structures of p65 C-terminal domain and its complex with stem IV of TER reveal that RNA recognition is achieved by a combination of single- and double-stranded RNA binding, which induces a 105° bend in TER. The domain is a cryptic, atypical RNA recognition motif with a disordered C-terminal extension that forms an α helix in the complex necessary for hierarchical assembly of TERT with p65-TER. This work provides the first structural insight into biogenesis and assembly of TER with a telomerase-specific protein. Additionally, our studies define a structurally homologous domain (xRRM) in genuine La and LARP7 proteins and suggest a general mode of RNA binding for biogenesis of their diverse RNA targets.
Department of Chemistry, and the Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095-1569, USA.
Mahavir
M
Singh
Zhonghua
Z
Wang
Bon-Kyung
BK
Koo
Anooj
A
Patel
Duilio
D
Cascio
Kathleen
K
Collins
Juli
J
Feigon
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018360:Crystallography, X-Ray; D024202:Electrophoretic Mobility Shift Assay; D020035:Holoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016053:RNA, Protozoan / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D019098:Telomerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016808:Tetrahymena thermophila / Q000201:enzymology / Q000235:genetics
D020035:Holoenzymes; D015800:Protozoan Proteins; D016053:RNA, Protozoan; D012261:Ribonucleoproteins; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase