Structural and biochemical studies of the distinct activity profiles of Rai1 enzymes.
Nucleic Acids Res
; 43(13): 6596-606, 2015 Jul 27.
Article
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| MEDLINE
| ID: mdl-26101253
ABSTRACT
Recent studies showed that Rai1 and its homologs are a crucial component of the mRNA 5'-end capping quality control mechanism. They can possess RNA 5'-end pyrophosphohydrolase (PPH), decapping, and 5'-3' exonuclease (toward 5' monophosphate RNA) activities, which help to degrade mRNAs with incomplete 5'-end capping. A single active site in the enzyme supports these apparently distinct activities. However, each Rai1 protein studied so far has a unique set of activities, and the molecular basis for these differences are not known. Here, we have characterized the highly diverse activity profiles of Rai1 homologs from a collection of fungal organisms and identified a new activity for these enzymes, 5'-end triphosphonucleotide hydrolase (TPH) instead of PPH activity. Crystal structures of two of these enzymes bound to RNA oligonucleotides reveal differences in the RNA binding modes. Structure-based mutations of these enzymes, changing residues that contact the RNA but are poorly conserved, have substantial effects on their activity, providing a framework to begin to understand the molecular basis for the different activity profiles.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Fúngicas
/
Proteínas de Unión al ARN
/
Endorribonucleasas
Límite:
Animals
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos