Structural and Functional Insights into Dom34, a Key Component of No-Go mRNA Decay

• Published in: Molecular cell 2007-09, Vol.27 (6), p.938-950
• Main Authors: Lee, Hyung Ho, Kim, Youn-Sung, Kim, Kyoung Hoon, Heo, Inha, Kim, Sang Kyu, Kim, Olesya, Kim, Hye Kyung, Yoon, Ji Young, Kim, Hyoun Sook, Kim, Do Jin, Lee, Sang Jae, Yoon, Hye Jin, Kim, Soon Jong, Lee, Byung Gil, Song, Hyun Kyu, Kim, V. Narry, Park, Chung-Mo, Suh, Se Won
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Archaeal Proteins - chemistry; Archaeal Proteins - metabolism; Binding Sites; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - metabolism; Endoribonucleases; Humans; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; Peptide Termination Factors - chemistry; Protein Structure, Quaternary; Protein Structure, Secondary; Ribonucleases - metabolism; RNA; RNA Stability; RNA, Messenger - chemistry; RNA, Messenger - metabolism; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism; Solutions; Structural Homology, Protein; Substrate Specificity; Thermoplasma - enzymology
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2007.07.019

The yeast protein Dom34 is a key component of no-go decay, by which mRNAs with translational stalls are endonucleolytically cleaved and subsequently degraded. However, the identity of the endoribonuclease is unknown. Homologs of Dom34, called Pelota, are broadly conserved in eukaryotes and archaea. To gain insights into the structure and function of Dom34/Pelota, we have determined the structure of Pelota from Thermoplasma acidophilum (Ta Pelota) and investigated the ribonuclease activity of Dom34/Pelota. The structure of Ta Pelota is tripartite, and its domain 1 has the RNA-binding Sm fold. We have discovered that Ta Pelota has a ribonuclease activity and that its domain 1 is sufficient for the catalytic activity. We also demonstrate that domain 1 of Dom34 has an endoribonuclease activity against defined RNA substrates containing a stem loop, which supports a direct catalytic role of yeast Dom34 in no-go mRNA decay.