The role of deadenylation in the degradation of unstable mRNAs in trypanosomes

Removal of the poly(A) tail is the first step in the degradation of many eukaryotic mRNAs. In metazoans and yeast, the Ccr4/Caf1/Not complex has the predominant deadenylase activity, while the Pan2/Pan3 complex may trim poly(A) tails to the correct size, or initiate deadenylation. In trypanosomes, t...

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Detalles Bibliográficos
Autores: Schwede, A., Manful, T., Jha, B.A., Helbig, C., Bercovich, N., Stewart, M., Clayton, C.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2009
País:Argentina
Institución:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
Repositorio:Biblioteca Digital (UBA-FCEN)
Idioma:inglés
OAI Identifier:paperaa:paper_03051048_v37_n16_p5511_Schwede
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_03051048_v37_n16_p5511_Schwede
Access Level:acceso abierto
Palabra clave:chromatin assembly factor 1
gene product
messenger RNA
protein EP
ribosome protein
unclassified drug
EP procyclin protein, Trypanosoma brucei
membrane protein
mRNA deadenylase
phosphoglycerate kinase
protozoal protein
ribonuclease
3' untranslated region
5' untranslated region
adenylation
article
controlled study
cytoplasm
gene amplification
gene sequence
nonhuman
priority journal
protein depletion
protein targeting
RNA degradation
RNA interference
Trypanosoma
animal
chemistry
drug antagonism
enzymology
genetics
genome
growth, development and aging
metabolism
physiology
RNA stability
Eukaryota
Metazoa
Animals
Cytoplasm
Genome, Protozoan
Membrane Glycoproteins
Phosphoglycerate Kinase
Protozoan Proteins
Ribonucleases
RNA Interference
RNA Stability
RNA, Messenger
Descripción
Sumario:Removal of the poly(A) tail is the first step in the degradation of many eukaryotic mRNAs. In metazoans and yeast, the Ccr4/Caf1/Not complex has the predominant deadenylase activity, while the Pan2/Pan3 complex may trim poly(A) tails to the correct size, or initiate deadenylation. In trypanosomes, turnover of several constitutively-expressed or long-lived mRNAs is not affected by depletion of the 5'-3' exoribonuclease XRNA, but is almost completely inhibited by depletion of the deadenylase CAF1. In contrast, two highly unstable mRNAs, encoding EP procyclin and a phosphoglycerate kinase, PGKB, accumulate when XRNA levels are reduced. We here show that degradation of EP mRNA was partially inhibited after CAF1 depletion. RNAi-targeting trypanosome PAN2 had a mild effect on global deadenylation, and on degradation of a few mRNAs including EP. By amplifying and sequencing degradation intermediates, we demonstrated that a reduction in XRNA had no effect on degradation of a stable mRNA encoding a ribosomal protein, but caused accumulation of EP mRNA fragments that had lost substantial portions of the 5' and 3' ends. The results support a model in which trypanosome mRNAs can be degraded by at least two different, partially independent, cytoplasmic degradation pathways attacking both ends of the mRNA. © 2009 The Author(s).